tbuckley/cabot-search huggingface dataset:
CPAP may reduce cardiovascular mortality in patients with OSA
Authors: Carl J Reynolds
Journal: Thorax (2012)

professionals, and clinical trials of treatment in older populations are vital if we are to ensure that all patients receive the very best care, regardless of their age.Contributors PB, RS, MDP and IW lead the team responsible for audit data.RH provided the initial idea for the analysis.PB analysed the data under the supervision of RBH and LJT.PB wrote the paper with substantial input from all authors on content, style and presentation.
Nitroglycerin Induces Late Preconditioning Against Myocardial Infarction in Conscious Rabbits Despite Development of Nitrate Tolerance
Authors: Michael Hill, Hitoshi Takano, Xian-Liang Tang, Eitaro Kodani, Gregg Shirk, Roberto Bolli
Journal: Circulation (2001)

Recent studies suggest that the late phase of ischemic preconditioning (PC) can be mimicked by pretreatment with NO donors. The ability of clinically relevant NO donors to induce PC against infarction, however, has not been evaluated. Furthermore, it is unknown whether tolerance to the hemodynamic actions of nitrates also extends to their PC effects.Conscious rabbits underwent a 30-minute coronary occlusion and 3 days of reperfusion. A 60-minute intravenous (IV) infusion of nitroglycerin (NTG) ending 1 hour before occlusion reduced infarct size, indicating an early PC effect. When the time interval between NTG infusion and occlusion was extended to 24 or 72 hours, the infarct-sparing action of NTG became even more pronounced, indicating a robust late PC effect. Transdermal NTG patches elicited a late PC effect that was (1) equivalent to that induced by IV NTG, demonstrating the efficacy of transdermal NTG as an alternative form of NTG delivery for inducing late PC, and (2) similar in nitrate-tolerant and -nontolerant rabbits, demonstrating that tolerance does not extend to the PC effects of NTG.In conscious rabbits, administration of NTG via either the IV or the transdermal route elicits a robust protective effect against infarction that lasts for 72 hours. The magnitude of NTG-induced cardioprotection is equivalent to that observed during the late phase of ischemic PC and is not affected by the development of tolerance. These findings reveal a new action of nitrates and support novel applications of these drugs for protecting the ischemic myocardium in patients.
Vitamin D and COPD: seasonal variation is important
Authors: S. N. Ampikaipakan, D. A. Hughes, J. C. Hughes, T. Amen, G. Bentham, A. M. Wilson
Journal: Thorax (2010)

Janssens et al 1 have demonstrated the relationship between vitamin D status and lung function in patients with chronic obstructive pulmonary disease (COPD). However, in their study there was only one assessment of vitamin D status per patient. Given the minimal component of diet to vitamin D status (serum 25-hydroxyvitamin D (25(OH)D) concentration),2 it is mostly determined by sunlight exposure and has a seasonal variation in healthy individuals.3

In a study of 24 patients with COPD (mean (SD) age 69 (5.8) years and smoking history 43 (15.8) pack-years) with measurements undertaken in the same individuals at the end of summer (August/September) and winter (March/April), we …
Effect of Tibolone on Breast Cancer Cell Proliferation in Postmenopausal ER+ Patients: Results from STEM Trial
Authors: Ernst Kubista, Juan V.M. Planellas Gomez, Mitch Dowsett, Jean-Michel Foidart, Kamil Pohlodek, Rudolphe Serreyn, Michail Nechushkin, Alexey G. Manikhas, Victor F. Semiglazov, Cornelius C.M. Hageluken, Christian F. Singer
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Tibolone is a selective tissue estrogenic activity regulator, approved for the treatment of vasomotor symptoms in postmenopausal women. We have done an exploratory, double-blind, randomized, placebo-controlled pilot trial to investigate the tissue-specific effects of 2.5 mg tibolone on breast cancer in postmenopausal women, in particular on tissue proliferation (STEM, Study of Tibolone Effects on Mamma carcinoma tissue). Experimental Design: Postmenopausal women with initially stage I/II, estrogen receptor–positive (ER+) primary breast cancer, were randomly assigned to 14 days of placebo or 2.5 mg/d tibolone. Core biopsies of the primary tumor were obtained before and after treatment. Ki-67 and apoptosis index were analyzed in baseline and corresponding posttreatment specimen. Results: Of 102 enrolled patients, 95 had evaluable data. Baseline characteristics were comparable between both treatment groups. Breast cancer cases are mainly invasive (99%), stage I or II (42% and 50% respectively), and ER+ (99%). Median intratumoral Ki-67 expression at baseline was 13.0% in the tibolone group and 17.8% in the placebo group, and decreased to 12.0% after 14 days of tibolone while increasing to 19.0% in the placebo group. This change from baseline was not significantly different between tibolone and placebo (Wilcoxon test; P = 0.17). A significant difference was observed between the treatment groups when the median change from baseline apoptosis index was compared between the treatment groups (tibolone, 0.0%; placebo, +0.3%; Wilcoxon test; P = 0.031). The incidence of adverse effects was comparable. Conclusions: In ER+ breast tumors, 2.5 mg/d tibolone given for 14 days has no significant effect on tumor cell proliferation.
Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial
Authors: Stephan Glund, Joachim Stangier, Michael Schmohl, Dietmar Gansser, Stephen Norris, Joanne van Ryn, Benjamin Lang, Steven Ramael, Viktoria Moschetti, Fredrik Gruenenfelder, Paul Reilly, Jörg Kreuzer
Journal: The Lancet (2015)
Tumor suppressor in lung cancer 1 (TSLC1) alters tumorigenic growth properties and gene expression
Authors: Thomas E Sussan, Mathew T Pletcher, Yoshinori Murakami, Roger H Reeves
Journal: Molecular Cancer (2005)

Abstract Background Introduction of cDNA or genomic clones of the tumor suppressor in lung cancer 1 ( TSLC1 ) gene into the non-small cell lung cancer line, A549, reverses tumorigenic growth properties of these cells. These results and the observation that TSLC1 is down-regulated in a number of tumors suggest that TSLC1 functions as a critical switch mediating repression of tumorigenesis. Results To investigate this mechanism, we compared growth properties of A549 with the TSLC1 -containing derivative. We found a G1/S phase transition delay in 12.2. Subtractive hybridization, quantitative PCR, and TranSignal Protein/DNA arrays were used to identify genes whose expression changed when TSLC1 was up-regulated. Members of common G1/S phase regulatory pathways such as TP53 , MYC , RB1 and HRAS were not differentially expressed, indicating that TSLC1 may function through an alternative pathway(s). A number of genes involved in cell proliferation and tumorigenesis were differentially expressed, notably genes in the Ras-induced senescence pathway. We examined expression of several of these key genes in human tumors and normal lung tissue, and found similar changes in expression, validating the physiological relevance of the A549 and 12.2 cell lines. Conclusion Gene expression and cell cycle differences provide insights into potential downstream pathways of TSLC1 that mediate the suppression of tumor properties in A549 cells.
Acvbp Versus Chop for Primary Large Cell Gastric Lymphoma
Authors: Imtinene Belaid, Nesrine Mejri, Imene Chabchoub, Rim Chafai, Faten Ezzairi, Leila Ben Fatma, Olfa Gharbi, Makrem Hochlaf, Slim Ben Ahmed
Journal: Annals of Oncology (2013)
Quinolone resistance among Escherichia coli strains from community-acquired urinary tract infections in Greece
Authors: S. Chaniotaki, P. Giakouppi, L.S. Tzouvelekis, D. Panagiotakos, M. Kozanitou, G. Petrikkos, A. Avlami, A.C. Vatopoulos
Journal: Clinical Microbiology and Infection (2004)
Peptic ulcer in hospital: An analysis of a 10% in-patient enquiry throughout England and Wales
Authors: H. D. Johnson
Journal: Gut (1962)

This study corresponds to an estimated 142,250 admissions for peptic ulcer to the wards of National Health Service hospitals in England and Wales during the two years 1956 and 1957. It presents a picture of the incidence and mortality of complications and surgical treatment throughout England and Wales.
Theophylline improves acute mountain sickness
Authors: R Fischer, SM Lang, U Steiner, M Toepfer, H Hautmann, H Pongratz, RM Huber
Journal: European Respiratory Journal (2000)

A randomized two-part study was conducted in order to determine the efficacy of theophylline in the treatment of acute mountain sickness during fast ascent to altitudes &gt;2,500 m. Fourteen healthy male subjects participated in a randomized single-blind placebo-controlled crossover study carried out in a decompression chamber (simulated altitude 4,500 m). A second randomized single-blind, placebo-controlled study was conducted at a high-altitude research laboratory (3,454 m) and included 21 healthy male subjects. The study medication was either 375 mg oral slow-release theophylline (250 mg if &lt;70 kg) or a matched placebo tablet taken twice daily. The acute mountain sickness score (AMSS) was assessed three times a day, beginning 18 h prior to altitude exposure and continuing for 18 h after altitude exposure. In addition, measurements of respiratory frequency, pulse rate, oxygen saturation and arterial blood gas levels were performed. Acute mountain sickness was significantly reduced by theophylline during the decompression chamber study (mean+/-SD 1.2+/-0.9) with placebo versus 3.6+/-0.8 with theophylline; p=0.03). During the high-altitude study, subjects with theophylline showed a significantly lower AMSS on arrival and after 18 h at altitude (0.6 versus 2.3, p=0.03). Oxygenation was improved in both parts of the study. In conclusion, oral slow-release theophylline improves acute mountain sickness.
Consciousness and emotions are minimized
Authors: Horacio Fabrega, Jr.
Journal: Behavioral and Brain Sciences (2004)

In the case of religion, explanations based on emotion should be privileged over those based on “cold” cognition. The origins of religious beliefs are as critical to understanding religion as are the group phenomena which sustain them. In addition, religion's relationship to the growth of knowledge is neglected by the target authors. The balance between the costs and benefits of religion will vary depending upon the phase of an individual society's cultural evolution.
Herpes Simplex Virus Us3(−) Mutant as Oncolytic Strategy and Synergizes with Phosphatidylinositol 3-Kinase-Akt–Targeting Molecular Therapeutics
Authors: Ta-Chiang Liu, Hiroaki Wakimoto, Robert L. Martuza, Samuel D. Rabkin
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Oncolytic herpes simplex virus (HSV) vectors have shown safety in clinical trials, but efficacy remains unsatisfactory. Novel HSV vectors that possess tumor selectivity with enhanced potency are therefore needed. The gene product of HSV Us3 protects virus-infected cells from apoptosis, a cellular pathway frequently dysfunctional in tumors. We hypothesized that Us3 mutants, whose replication would be inhibited by apoptosis in normal cells, would be selective for tumor cells. Experimental Design: HSV mutants G207 (ribonucleotide reductase−/γ34.5−), R7041 (Us3−), and R7306 (Us3 revertant) were tested in normal and tumor cells for viral replication, antitumoral potency, apoptosis induction, and Akt activation. Safety and biodistribution after systemic administration and antitumoral efficacy after intratumoral (i.t.) or i.v. administration were examined. Results: Us3 deletion results in up to 3-log replication inhibition in normal cells, which correlates with enhanced apoptosis induction. In contrast, R7041 replicates very well in tumor cells, showing 1 to 2 log greater yield than G207. In vivo, R7041 shows no signs of toxicity after systemic delivery in both immunocompetent and immunodeficient mice and shows preferential and prolonged replication in tumors compared with normal tissues. R7041 displays significant antitumoral efficacy after i.t. or i.v. administration. An additional feature of Us3 mutants is enhanced Akt activation compared with wild-type infection, which sensitizes cells to phosphatidylinositol 3-kinase-Akt inhibitors (LY294002, Akt inhibitor IV), shown by synergistic antitumoral activity in vitro and enhanced efficacy in vivo. Conclusions: Us3 deletion confers enhanced tumor selectivity and antitumoral potency on herpes simplex virus-1 and provides for a novel mechanism of combination therapy with phosphatidylinositol 3-kinase-Akt–targeting molecular therapeutics.
Carpenter and Dukes Fund
Authors: M. Chas. Dukes
Journal: BMJ (1892)

Gonadal dysgenesis and Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) are the most common causes of primary amenorrhoea. Patients with gonadal dysgenesis present with primary amenorrhoea and lack of secondary sexual characteristics, which, in contrast, are present in patients with MRKHS. The coexistence of the 2 syndromes has been reported in only a few studies so far. We describe a case of a 15-year-old girl who presented with short stature and primary amenorrhoea. Investigations revealed hypergonadotropic hypogonadism, and absence of the uterus, and upper two-thirds of the vagina, with presence of the rudimentary lower third of the vagina and non-visualised bilateral ovaries on imaging. Karyotyping obtained by lymphocyte culture GTG banding revealed 45X/46XX. The patient was diagnosed as having a rare case of gonadal dysgenesis with MRKH. She was started on growth hormone therapy. The association of these syndromes is uncommon, and has further implications on fertility and pregnancy, affecting the quality of life.
Synthetic Biology: An Emerging Engineering Discipline
Authors: Allen A. Cheng, Timothy K. Lu
Journal: Annual Review of Biomedical Engineering (2012)

Over the past decade, synthetic biology has emerged as an engineering discipline for biological systems. Compared with other substrates, biology poses a unique set of engineering challenges resulting from an incomplete understanding of natural biological systems and tools for manipulating them. To address these challenges, synthetic biology is advancing from developing proof-of-concept designs to focusing on core platforms for rational and high-throughput biological engineering. These platforms span the entire biological design cycle, including DNA construction, parts libraries, computational design tools, and interfaces for manipulating and probing synthetic circuits. The development of these enabling technologies requires an engineering mindset to be applied to biology, with an emphasis on generalizable techniques in addition to application-specific designs. This review aims to discuss the progress and challenges in synthetic biology and to illustrate areas where synthetic biology may impact biomedical engineering and human health.
First-line single-agent cetuximab in patients with advanced colorectal cancer
Authors: A. Pessino, S. Artale, S. Sciallero, A. Guglielmi, G. Fornarini, I.C. Andreotti, S. Mammoliti, D. Comandini, F. Caprioni, E. Bennicelli, V. Andretta, S. Siena, A. Sobrero
Journal: Annals of Oncology (2007)
The Synovial Sarcoma–Associated SS18-SSX2 Fusion Protein Induces Epigenetic Gene (De)Regulation
Authors: Diederik R.H. de Bruijn, Susanne V. Allander, Anke H.A. van Dijk, Marieke P. Willemse, Jose Thijssen, Jan J.M. van Groningen, Paul S. Meltzer, Ad Geurts van Kessel
Journal: Cancer Research (2006)

Abstract Fusion of the SS18 and either one of the SSX genes is a hallmark of human synovial sarcoma. The SS18 and SSX genes encode nuclear proteins that exhibit opposite transcriptional activities. The SS18 protein functions as a transcriptional coactivator and is associated with the SWI/SNF complex, whereas the SSX proteins function as transcriptional corepressors and are associated with the polycomb complex. The domains involved in these opposite transcriptional activities are retained in the SS18-SSX fusion proteins. Here, we set out to determine the direct transcriptional consequences of conditional SS18-SSX2 fusion protein expression using complementary DNA microarray-based profiling. By doing so, we identified several clusters of SS18-SSX2–responsive genes, including a group of genes involved in cholesterol synthesis, which is a general characteristic of malignancy. In addition, we identified a group of SS18-SSX2–responsive genes known to be specifically deregulated in primary synovial sarcomas, including IGF2 and CD44. Furthermore, we observed an uncoupling of EGR1, JUNB, and WNT signaling in response to SS18-SSX2 expression, suggesting that the SWI/SNF-associated coactivation functions of the SS18 moiety are impaired. Finally, we found that SS18-SSX2 expression affects histone modifications in the CD44 and IGF2 promoters and DNA methylation levels in the IGF2 imprinting control region. Together, we conclude that the SS18-SSX2 fusion protein may act as a so-called transcriptional “activator-repressor,” which induces downstream target gene deregulation through epigenetic mechanisms. Our results may have implications for both the development and clinical management of synovial sarcomas. (Cancer Res 2006; 66(19): 9474-82)
Safety, Pharmacokinetics, and Preliminary Clinical Activity of Inotuzumab Ozogamicin, a Novel Immunoconjugate for the Treatment of B-Cell Non-Hodgkin's Lymphoma: Results of a Phase I Study
Authors: Anjali Advani, Bertrand Coiffier, Myron S. Czuczman, Martin Dreyling, James Foran, Eva Gine, Christian Gisselbrecht, Nicolas Ketterer, Sunita Nasta, Ama Rohatiner, Ingo G.H. Schmidt-Wolf, Martin Schuler, Jorge Sierra, Mitchell R. Smith, Gregor Verhoef, Jane N. Winter, Joseph Boni, Erik Vandendries, Mark Shapiro, Luis Fayad
Journal: Journal of Clinical Oncology (2010)

PURPOSE Inotuzumab ozogamicin (CMC-544) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. This was a phase I study to determine the maximum-tolerated dose (MTD), safety, and preliminary efficacy of inotuzumab ozogamicin in an expanded MTD cohort of patients with relapsed or refractory CD22(+) B-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Inotuzumab ozogamicin was administered intravenously as a single agent once every 3 or 4 weeks at doses ranging from 0.4 to 2.4 mg/m(2). Outcomes included MTD, safety, pharmacokinetics, response, progression-free survival (PFS), and overall survival. Results Seventy-nine patients were enrolled. The MTD was determined to be 1.8 mg/m(2). Common adverse events at the MTD were thrombocytopenia (90%), asthenia (67%), and nausea and neutropenia (51% each). The objective response rate at the end of treatment was 39% for the 79 enrolled patients, 68% for all patients with follicular NHL treated at the MTD, and 15% for all patients with diffuse large B-cell lymphoma treated at the MTD. Median PFS was 317 days (approximately 10.4 months) and 49 days for patients with follicular NHL and diffuse large B-cell lymphoma, respectively. CONCLUSION Inotuzumab ozogamicin has demonstrated efficacy against CD22(+) B-cell NHL, with reversible thrombocytopenia as the main toxicity.
Genetic instability in patients with Hodgkin's disease undergoing chemotherapy.
Authors: J M Abdallah, D P Lombardi, I R Kirsch
Journal: Journal of Clinical Investigation (1995)

We have studied the effect of chemotherapy on the level of a particular kind of genetic instability in patients with Hodgkin's disease. The particular type of genetic instability assayed is exemplified by trans-rearrangements between two (rather than within one) T cell antigen receptor. 16 patients were studied during their course of treatment. Presentation samples were available for 13 of these patients; 9 of them showed an increase in the level of trans-rearrangements during their exposure to chemotherapeutic agents (P < 0.043). All patients for whom posttherapy samples were available (10 out of 16) showed a return to baseline levels of trans-rearrangements 1-5 mo after completion of therapy (P < 0.03). Thus, this assay appears to be a marker for the "destabilizing" effects of certain chemotherapeutic agents.
Participation of Patients 65 Years of Age or Older in Cancer Clinical Trials
Authors: Joy H. Lewis, Meredith L. Kilgore, Dana P. Goldman, Edward L. Trimble, Richard Kaplan, Michael J. Montello, Michael G. Housman, José J. Escarce
Journal: Journal of Clinical Oncology (2003)

Although 61% of new cases of cancer occur among the elderly, recent studies indicate that the elderly comprise only 25% of participants in cancer clinical trials. Further investigation into the reasons for low elderly participation is warranted. Our objective was to evaluate the participation of the elderly in clinical trials sponsored by the National Cancer Institute (NCI) and assess the impact of protocol exclusion criteria on elderly participation.We conducted a retrospective analysis using NCI data, analyzing patient and trial characteristics for 59,300 patients enrolled onto 495 NCI-sponsored, cooperative group trials, active from 1997 through 2000. Our main outcome measure was the proportion of elderly patients enrolled onto cancer clinical trials compared with the proportion of incident cancer patients who are elderly.Overall, 32% of participants in phase II and III clinical trials were elderly, compared with 61% of patients with incident cancers in the United States who are elderly. The degree of underrepresentation was more pronounced in trials for early-stage cancers than in trials for late-stage cancers (P <.001). Furthermore, protocol exclusion criteria on the basis of organ-system abnormalities and functional status limitations were associated with lower elderly participation. We estimate that if protocol exclusions were relaxed, elderly participation in cancer trials would be 60%.The elderly are underrepresented in cancer clinical trials relative to their disease burden. Older patients are more likely to have medical histories that make them ineligible for clinical trials because of protocol exclusions. Insurance coverage for clinical trials is one step toward improvement of elderly access to clinical trials. Without a change in study design or requirements, this step may not be sufficient.
Arterial stiffness in Behcet's disease: increased regional pulse wave velocity values
Authors: H K Chang
Journal: Annals of the Rheumatic Diseases (2006)

Diverse vascular lesions occur in about one third of patients with Behcet’s disease (BD). Endothelial dysfunction is known to have an important role in the development of these lesions.1 Acute systemic inflammation and chronic systemic vasculitis are associated with endothelial dysfunction.2,3 Moreover, inflammation is an important risk factor for future cardiovascular events.4 These findings have led to the hypothesis that acute and chronic inflammatory processes associated with BD may cause endothelial dysfunction, which can then lead to a subsequent increase of arterial stiffness and vascular damage that are closely related to the clinical course of BD. Arterial stiffness is a reliable predictor of subsequent cardiovascular mortality and vascular damage. Pulse wave velocity (PWV) is an ideal indicator of arterial stiffness.5,6 …