tbuckley/cabot-search huggingface dataset:
Impact of Cardioselective β-Blockers on Mortality in Patients with Chronic Obstructive Pulmonary Disease and Atherosclerosis
Authors: Yvette R. B. M. van Gestel, Sanne E. Hoeks, Don D. Sin, Gijs M. J. M. Welten, Olaf Schouten, Han J. Witteveen, Cihan Simsek, Henk Stam, Frans W. Mertens, Jeroen J. Bax, Ron T. van Domburg, Don Poldermans
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

beta-Blocker use is associated with improved health outcomes in patients with cardiovascular disease. There is a general reluctance to prescribe beta-blockers in patients with chronic obstructive pulmonary disease (COPD) because they may worsen symptoms.We investigated the relationship between cardioselective beta-blockers and mortality in patients with COPD undergoing major vascular surgery.We evaluated 3,371 consecutive patients who underwent major vascular surgery at one academic institution between 1990 and 2006. The patients were divided into those with and without COPD on the basis of symptoms and spirometry. The major endpoints were 30-day and long-term mortality after vascular surgery. Patients were defined as receiving low-dose therapy if the dosage was less than 25% of the maximum recommended therapeutic dose; dosages higher than this were defined as intensified dose.There were 1,205 (39%) patients with COPD of whom 462 (37%) received cardioselective beta-blocking agents. beta-Blocker use was associated independently with lower 30-day (odds ratio, 0.37; 95% confidence interval, 0.19-0.72) and long-term mortality in patients with COPD (hazards ratio, 0.73; 95% confidence interval, 0.60-0.88). Intensified dose was associated with both reduced 30-day and long-term mortality in patients with COPD, whereas low dose was not.Cardioselective beta-blockers were associated with reduced mortality in patients with COPD undergoing vascular surgery. In carefully selected patients with COPD, the use of cardioselective beta-blockers appears to be safe and associated with reduced mortality.
Molecular Genetics of Acute Lymphoblastic Leukemia
Authors: Michael A. Teitell, Pier Paolo Pandolfi
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

Acute lymphoblastic leukemia (ALL) is mainly a disease of childhood that arises from recurrent genetic insults that block precursor B and T cell differentiation and drive aberrant cell proliferation and survival. Recurrent defects including chromosomal translocations, aneuploidies, and gene-specific alterations generate molecular subgroups of B- and T-ALL with differing clinical courses and distinct responses to therapy. Recent discoveries arising from genome-wide surveys and adoptive transfer of leukemia-initiating cells have uncovered multiple gene copy number aberrations and have yielded new insight into at least one type of ALL-originating cell. Our understanding of the pathogenesis of ALL has benefited from genetically modified mouse models that recapitulate cellular transformation at specific developmental stages of lymphoid lineage cells. Here, we review the spectrum of genetic aberrations that promote acute B and T cell leukemias and the mechanisms of cell transformation and malignant progression that are reinforced by mouse models of human ALL.
Modelling criteria: Not just for robots
Authors: George N. Reeke
Journal: Behavioral and Brain Sciences (2001)

Webb's scheme for classifying behavioral models is applicable to a wide range of theories and simulations, nonrobotic as well as robotic. It is suggested that a meta-analysis of existing models, characterized according to the proposed scheme, could identify regions of the seven-dimensional modelling space that are particularly likely to lead to new insights in understanding behavior.
Remarks on the Mechanical Treatment of Uterine Displacements and Flexions
Authors: J. G. S. Coghill
Journal: BMJ (1881)

present seems a favourable time for re-opening the consideration of what we may term briefly uterine mechanics.Professional opinion is still divided tipon this much vexed question; but there are indica- tions that it is undergoing a change.Gynoecologists are still far from being agreed even as to the propriety, much less as to the exact nature, of the mechanical treatment to be employed in this large, important, and interesting class of cases.We have two extremes of opinion as to the clinical importance of uterine displacements and distortions.Accord- ing to the one, these conditions are always the active or potential source of grave local and general troubles, and should therefore be at once brought under treatment, mainly of a local and mechanical character; according to the other extreme, the conditions in question are to be regarded simply as the passive local expression of troubles to be looked for and treated elsewhere, either in ovarian irritation or in dis- ordered states of general health.It is greatly to be regretted that not only have opinions in regard to these questions been too extreme, but sentiment, if not personal feeling, has too evidently prevailed in their expression.When trustworthy evidence is adduced in support of certain views as to matters of common interest, it is the duty of those who incline to another opinion to examine carefully and with unbiassed mind the facts stated, to judge of them calmly, and express themselves temperately.But to ignore, to refuse to investigate, and to assert dogmatically contrary opinions, is neither courteous nor scientific.No progress is possible in any direction, were this the attitude and method adopted.Prejuclice, unfortunately, has, in this as in other important questions, interfered too often with calm judgment, and has induced an attitude of incredulity and tone of opposition at once unreasonable and unscientific.
Diabetes as a Cause of Clinically Significant Functional Cobalamin Deficiency
Authors: Lawrence R. Solomon
Journal: Diabetes Care (2011)

Functional cobalamin (Cbl) deficiency (i.e., high methylmalonic acid [MMA] values despite normal serum Cbl levels) is common in the elderly and associated with neuropathy and anemia. Because diabetes is also common in the elderly and diabetic neuropathy resembles that of Cbl deficiency, the role of diabetes in functional Cbl deficiency was explored.A retrospective review was performed of all ambulatory community-dwelling adults with normal renal function evaluated for Cbl deficiency over a 12-year period in a primary care setting. Functional Cbl deficiency was defined as MMA values >250 nmol/L with Cbl levels >400 pg/mL.In nondiabetic subjects, MMA values varied directly with age and inversely with serum Cbl. In diabetic subjects, MMA values also increased with age but did not fall as Cbl levels increased. Thus, when Cbl levels were >400 pg/mL, mean MMA values and the incidence of functional Cbl deficiency were both significantly greater in elderly diabetic subjects (at least 70 years old) than in elderly nondiabetic subjects. Moreover, neuropathy was present in 62% of diabetic subjects with high MMA values and in only 18% of diabetic subjects with normal MMA values. Finally, pharmacologic doses of Cbl improved MMA values and neuropathy in 88 and 86% of evaluable diabetic subjects, respectively.These observations suggest that functional Cbl deficiency is common in elderly diabetic individuals, is associated with neuropathy, and is responsive to Cbl therapy. A role for oxidative stress in the pathogenesis of functional Cbl deficiency is proposed.
Salivary Gland Tumors in Transgenic Mice with Targeted <i>PLAG1</i> Proto-Oncogene Overexpression
Authors: Jeroen Declercq, Frederik Van Dyck, Caroline V. Braem, Isabelle C. Van Valckenborgh, Marianne Voz, Michel Wassef, Luc Schoonjans, Boudewijn Van Damme, Laurence Fiette, Wim J.M. Van de Ven
Journal: Cancer Research (2005)

Pleomorphic adenoma gene 1 (PLAG1) proto-oncogene overexpression is implicated in various human neoplasias, including salivary gland pleomorphic adenomas. To further assess the oncogenic capacity of PLAG1, two independent PLAG1 transgenic mouse strains were established, PTMS1 and PTMS2, in which activation of PLAG1 overexpression is Cre mediated. Crossbreeding of PTMS1 or PTMS2 mice with MMTV-Cre transgenic mice was done to target PLAG1 overexpression to salivary and mammary glands, in the P1-Mcre/P2-Mcre offspring. With a prevalence of 100% and 6%, respectively, P1-Mcre and P2-Mcre mice developed salivary gland tumors displaying various pleomorphic adenoma features. Moreover, histopathologic analysis of salivary glands of 1-week-old P1-Mcre mice pointed at early tumoral stages in epithelial structures. Malignant characteristics in the salivary gland tumors and frequent lung metastases were found in older tumor-bearing mice. PLAG1 overexpression was shown in all tumors, including early tumoral stages. The tumors revealed an up-regulation of the expression of two distinct, imprinted gene clusters (i.e., Igf2/H19 and Dlk1/Gtl2). With a latency period of about 1 year, 8% of the P2-Mcre mice developed mammary gland tumors displaying similar histopathologic features as the salivary gland tumors. In conclusion, our results establish the strong and apparently direct in vivo tumorigenic capacity of PLAG1 and indicate that the transgenic mice constitute a valuable model for pleomorphic salivary gland tumorigenesis and potentially for other glands as well.
Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies
Authors: Guillermo F. Sanz, Silvana Saavedra, Dolores Planelles, Leonor Senent, Jose Cervera, Eva Barragán, Carmen Jiménez, Luis Larrea, Guillermo Martı́n, Jesús Martı́nez, Isidro Jarque, Federico Moscardó, Gemma Plumé, Rafael Andreu, Ana I. Regadera, Inmaculada Garcı́a, Susana Mollá, Pilar Solves, Javier de la Rubia, Pascual Bolufer, Luis Benlloch, Marı́a A. Soler, Marı́a L. Marty, Miguel A. Sanz
Journal: Blood (2001)
Denosumab and Bone Metastasis–Free Survival in Men With Nonmetastatic Castration-Resistant Prostate Cancer: Exploratory Analyses by Baseline Prostate-Specific Antigen Doubling Time
Authors: Matthew R. Smith, Fred Saad, Stephane Oudard, Neal Shore, Karim Fizazi, Paul Sieber, Bertrand Tombal, Ronaldo Damiao, Gavin Marx, Kurt Miller, Peter Van Veldhuizen, Juan Morote, Zhishen Ye, Roger Dansey, Carsten Goessl
Journal: Journal of Clinical Oncology (2013)

Purpose Denosumab, an anti–RANK ligand monoclonal antibody, significantly increases bone metastasis–free survival (BMFS; hazard ratio [HR], 0.85; P = .028) and delays time to first bone metastasis in men with nonmetastatic castration-resistant prostate cancer (CRPC) and baseline prostate-specific antigen (PSA) ≥ 8.0 ng/mL and/or PSA doubling time (PSADT) ≤ 10.0 months. To identify men at greatest risk for bone metastasis or death, we evaluated relationships between PSA and PSADT with BMFS in the placebo group and the efficacy and safety of denosumab in men with PSADT ≤ 10, ≤ 6, and ≤ 4 months. Patients and Methods A total of 1,432 men with nonmetastatic CRPC were randomly assigned 1:1 to monthly subcutaneous denosumab 120 mg or placebo. Enrollment began February 2006; primary analysis cutoff was July 2010, when approximately 660 men were anticipated to have developed bone metastases or died. Results In the placebo group, shorter BMFS was observed as PSADT decreased below 8 months. In analyses by shorter baseline PSADT, denosumab consistently increased BMFS by a median of 6.0, 7.2, and 7.5 months among men with PSADT ≤ 10 (HR, 0.84; P = .042), ≤ 6 (HR, 0.77; P = .006), and ≤ 4 months (HR, 0.71; P = .004), respectively. Denosumab also consistently increased time to bone metastasis by PSADT subset. No difference in survival was observed between treatment groups for the overall study population or PSADT subsets. Conclusion Patients with shorter PSADT are at greater risk for bone metastasis or death. Denosumab consistently improves BMFS in men with shorter PSADT and seems to have the greatest treatment effects in men at high risk for progression.
Combination Long-Acting β-Agonists and Inhaled Corticosteroids Compared With Long-Acting β-Agonists Alone in Older Adults With Chronic Obstructive Pulmonary Disease
Authors: Andrea S. Gershon, Michael A. Campitelli, Ruth Croxford, Matthew B. Stanbrook, Teresa To, Ross Upshur, Anne L. Stephenson, Thérèse A. Stukel
Journal: JAMA (2014)

<h3>Importance</h3> Chronic obstructive pulmonary disease (COPD), a manageable respiratory condition, is the third leading cause of death worldwide. Knowing which prescription medications are the most effective in improving health outcomes for people with COPD is essential to maximizing health outcomes. <h3>Objective</h3> To estimate the long-term benefits of combination long-acting β-agonists (LABAs) and inhaled corticosteroids compared with LABAs alone in a real-world setting. <h3>Design, Setting, and Patients</h3> Population-based, longitudinal cohort study conducted in Ontario, Canada, from 2003 to 2011. All individuals aged 66 years or older who met a validated case definition of COPD on the basis of health administrative data were included. After propensity score matching, there were 8712 new users of LABA–inhaled corticosteroid combination therapy and 3160 new users of LABAs alone who were followed up for median times of 2.7 years and 2.5 years, respectively. <h3>Exposures</h3> Newly prescribed combination LABAs and inhaled corticosteroids or LABAs alone. <h3>Main Outcomes and Measures</h3> Composite outcome of death and COPD hospitalization. <h3>Results</h3> The main outcome was observed among 5594 new users of LABAs and inhaled corticosteroids (3174 deaths [36.4%]; 2420 COPD hospitalizations [27.8%]) and 2129 new users of LABAs alone (1179 deaths [37.3%]; 950 COPD hospitalizations [30.1%]). New use of LABAs and inhaled corticosteroids was associated with a modestly reduced risk of death or COPD hospitalization compared with new use of LABAs alone (difference in composite outcome at 5 years, −3.7%; 95% CI, −5.7% to −1.7%; hazard ratio [HR], 0.92; 95% CI, 0.88-0.96). The greatest difference was among COPD patients with a codiagnosis of asthma (difference in composite at 5 years, −6.5%; 95% CI, −10.3% to −2.7%; HR, 0.84; 95% CI, 0.77-0.91) and those who were not receiving inhaled long-acting anticholinergic medication (difference in composite at 5 years, −8.4%; 95% CI, −11.9% to −4.9%; HR, 0.79; 95% CI, 0.73-0.86). <h3>Conclusions and Relevance</h3> Among older adults with COPD, particularly those with asthma and those not receiving a long-acting anticholinergic medication, newly prescribed LABA and inhaled corticosteroid combination therapy, compared with newly prescribed LABAs alone, was associated with a significantly lower risk of the composite outcome of death or COPD hospitalization.
Multiple Gene Expression Classifiers from Different Array Platforms Predict Poor Prognosis of Colorectal Cancer
Authors: Yu-Hsin Lin, Jan Friederichs, Michael A. Black, Jörg Mages, Robert Rosenberg, Parry J. Guilford, Vicky Phillips, Mark Thompson-Fawcett, Nikola Kasabov, Tumi Toro, Arend E. Merrie, Andre van Rij, Han-Seung Yoon, John L. McCall, Jörg Rüdiger Siewert, Bernhard Holzmann, Anthony E. Reeve
Journal: Clinical Cancer Research (2007)

Abstract Purpose: This study aimed to develop gene classifiers to predict colorectal cancer recurrence. We investigated whether gene classifiers derived from two tumor series using different array platforms could be independently validated by application to the alternate series of patients. Experimental Design: Colorectal tumors from New Zealand (n = 149) and Germany (n = 55) patients had a minimum follow-up of 5 years. RNA was profiled using oligonucleotide printed microarrays (New Zealand samples) and Affymetrix arrays (German samples). Classifiers based on clinical data, gene expression data, and a combination of the two were produced and used to predict recurrence. The use of gene expression information was found to improve the predictive ability in both data sets. The New Zealand and German gene classifiers were cross-validated on the German and New Zealand data sets, respectively, to validate their predictive power. Survival analyses were done to evaluate the ability of the classifiers to predict patient survival. Results: The prediction rates for the New Zealand and German gene-based classifiers were 77% and 84%, respectively. Despite significant differences in study design and technologies used, both classifiers retained prognostic power when applied to the alternate series of patients. Survival analyses showed that both classifiers gave a better stratification of patients than the traditional clinical staging. One classifier contained genes associated with cancer progression, whereas the other had a large immune response gene cluster concordant with the role of a host immune response in modulating colorectal cancer outcome. Conclusions: The successful reciprocal validation of gene-based classifiers on different patient cohorts and technology platforms supports the power of microarray technology for individualized outcome prediction of colorectal cancer patients. Furthermore, many of the genes identified have known biological functions congruent with the predicted outcomes.
Exhaled breath temperature in COPD patients
Authors: Gabriel Garcia, Miguel Bergna, Orlando Lopez Jové
Journal: European Respiratory Journal (2012)

Introduction: Chronic obstructive pulmonary disease (COPD) is a common airway inflammatory disorder with structural degradation of the airway tissue. Previous reports showed that patients with COPD had EBT lower than normal subjects. Recently, a new combined COPD assessment was established based on the symptoms, spirometric classification and risk of exacerbation (GOLD 2011).  Objectives: Evaluate the EBT in COPD patients according to the new combined COPD assessment and compare to healthy subjects. Methods: EBT was measured (using the X-halo, Delmedica, Singapore) in 80 COPD patients (FEV1% 54±14, age 60±8 years, 46 males) and 80 healthy controls. Lung function, COPD Assessment Test (CAT), exacerbations and previous treatment was performed.  Results: There was not differences EBT between COPD patients 34,2°C vs healthy subjects 33,9°C. There was no correlation between EBT with FEV1% (r=0,23) and EBT with CAT (r=0,01) but patients with previous exacerbations had EBT more than patients without exacerbations (34,7°C vs 33,9°C, p  Conclusion: Our results showed that COPD patients with frequent exacerbations, 2 or more per year, had increased of Exhaled Breath Temperature, therefore may reflect inflammation in the COPD lung.
Staining in Gastrointestinal Endoscopy: Clinical Application and Limitations
Authors: C. S. Shim
Journal: Endoscopy (1999)

The fine detail of the structure of the gastrointestinal mucosa is not delineated during conventional endoscopy. Yamakawa et al. [1] reported in 1966 that spraying a blue dye solution over gastric mucosa was useful in revealing such structures as the areae gastricae. However, the results with this method were not always satisfactory, because gastric mucosa was also colored by the dye. In 1972 Ida et al. [2] reported a new procedure for eliminating gastric mucus. Using these techniques, the results of dye-spraying are consistently effective.
TRANSIENT NEUROLOGICAL SYMPTOMS ACCOMPANYING ECT
Authors: FRANCIS J. KANE
Journal: American Journal of Psychiatry (1963)

A case is reported of a 56-year-old psychotically depressed woman with severe vascular disease who suffered a transient hemiparesis after her third ECT. Her neurological picture cleared almost completely, and she later received 11 further ECTs with a good remission of her psychosis. No further neurological sequelae were noted, and she is well 9 months after discharge.
<i>p63</i>in Epithelial Survival, Germ Cell Surveillance, and Neoplasia
Authors: Christopher P. Crum, Frank D. McKeon
Journal: Annual Review of Pathology Mechanisms of Disease (2010)

The p53homolog p63has emerged as a gene with an enormously complex function that is distinct from that of p53. It encodes two distinct transcript isoforms that have a dramatic impact on replenishment of cutaneous epithelial stem cells and on ovarian germ cell survival. However, although these two fundamental roles of p63 attest to its powerful place in development, its other functions—specifically the apparent capacity of p63, when induced, to supervise the emergence of new cell populations in the breast, prostate, cervix, and upper reproductive tract—are shared by embryo and adult. These observed functions may only scratch the surface of a repertoire that has been postulated to encompass a range of cellular activities, as evidenced by the fact that p63 proteins have been shown to potentially bind to over 5800 target sites. Whether tumorigenic pathways are also involved, and to what extent, is a subject of both promise and controversy that remains to be resolved.
Cholestatic Hepatitis Associated With Repaglinide
Authors: Francisco López-García, Joaquín Borrás, Clara Verdú, V.R. Salazar, J. Antonio Ruiz, Jorge Sales, Mª Isabel Lucena, Raúl J. Andrade
Journal: Diabetes Care (2005)

Repaglinide is a fast, short-acting meglitinide analog antidiabetic drug approved for the treatment of type 2 diabetes. Hypoglycemia is a major adverse effect of this drug (1). In rare cases, elevated liver enzymes have been noted (2). We report a patient who developed cholestatic hepatitis while taking repaglinide.

A 72-year-old man had a 2-year history of type 2 diabetes that was initially controlled by diet. He had normal liver function. Two months before presentation, he began taking repaglinide (1 mg/day), and 1 month before presentation, the daily dose was increased to 2 mg. The patient presented because of a 2-week history …
Pathogenesis of gall stones in Crohn's disease: an alternative explanation.
Authors: R Hutchinson, P N Tyrrell, D Kumar, J A Dunn, J K Li, R N Allan
Journal: Gut (1994)

The increased prevalence of gall stones in Crohn's disease is thought to be related to depletion of the bile salt pool due either to terminal ileal disease or after ileal resection. This study was designed to examine whether this hypothesis is correct and explore alternative explanations. Two hundred and fifty one randomly selected patients (156 females, 95 males, mean age 45 years) were interviewed and screened by ultrasonography to determine the prevalence of gall stones in a large population of patients with Crohn's disease. Sixty nine (28%) patients had gall stones proved by ultrasonography (n = 42), or had had cholecystectomy for gall stone disease (n = 27). The risk factors for the development of gall stones including sex, age, site, and duration of disease, and previous intestinal resection were examined by multivariate analysis. Age and duration of disease were positive risk factors for gall stones and were covariables. The site of disease and of previous intestinal resection did not predispose to gall stones. Previous surgery was an independent risk factor for the development of gall stones, the risk increasing with number of laparotomies. It is suggested that mechanisms other than ileal dysfunction may predispose to gall stones. Postoperative gall bladder hypomotility with biliary sludge formation may be precursors of gall stone formation in patients with Crohn's disease.