tbuckley/cabot-search huggingface dataset:
Abstract 2198: A literature-based sum score of genetic variants in IGF genes modifies associations between indicators of energy balance and colorectal cancer risk
Authors: Colinda CJM Simons, Leo J. Schouten, Roger Godschalk, Frederik-Jan van Schooten, Piet A. van den Brandt, Matty P. Weijenberg
Journal: Cancer Research (2014)

Abstract Background: Gene-environment interactions between variants in growth-regulating IGF genes and energy balance in colorectal cancer (CRC) were studied in the Netherlands Cohort Study (NLCS) after 16.3 years follow-up. Methods: Using a systematic strategy, we selected 25 SNPs and a CA repeat in IGF genes that had repeatedly demonstrated significant associations with CRC risk, energy balance-related exposures or related endpoints in literature, and thus likely modify effects of energy balance on CRC development. Twenty-four SNPs were successfully genotyped in toenail DNA of NLCS subcohort members (n=3,203) and CRC cases (n=2,274) with adequate exposure data. Unfavorable alleles were aggregated into a sum score. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated in case-cohort analyses for linear combinations between tertiles of the genetic sum score and 8 energy balance-related exposures. Results: Significant and increasingly higher risks were observed for men with more adverse profiles compared to men with the most optimal profile. In particular carrying more unfavorable alleles in combination with a larger adult trouser/skirt size, an increased height or the absence of early life energy restriction during the Dutch Hunger Winter (1944-45) was associated with distal colon cancer [highest vs. lowest linear combinations: HR (95% CI) = 2.03 (1.27-3.24), 2.05 (1.16-3.63) and 1.87 (1.11-3.16), respectively]. A combined effect of IGF polymorphisms and energy balance-related exposures on subsite-specific CRC risk was less convincing in women. Conclusion: Combined effects of IGF polymorphisms and specific energy balance-related exposures are important in CRC development in men, and less convincingly in women. The availability of extensive environmental data and the aggregation of genetic variants were invaluable for interpreting the joint associations. Note: This abstract was not presented at the meeting. Citation Format: Colinda CJM Simons, Leo J. Schouten, Roger Godschalk, Frederik-Jan van Schooten, Piet A. van den Brandt, Matty P. Weijenberg. A literature-based sum score of genetic variants in IGF genes modifies associations between indicators of energy balance and colorectal cancer risk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2198. doi:10.1158/1538-7445.AM2014-2198
Invited commentary on the December Controversy articles by R Pabla: Nitric oxide and cardiovascular disease
Authors: R. Pabla
Journal: Cardiovascular Research (1994)

Journal Article Invited commentary on the December Controversy articles by R Pabla: Nitric oxide and cardiovascular disease Get access Ravinder Pabla Ravinder Pabla Pharmacology Department, King's College London, London SW3. UK. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 3, March 1994, Page 432, https://doi.org/10.1093/cvr/28.3.432 Published: 01 March 1994
How Do Small Molecules Do Great Things?
Authors: Reinhold Benesch
Journal: New England Journal of Medicine (1969)

In 1925 Greenwald discovered considerable quantities of 2,3-diphosphoglycerate (DPG) in mammalian red cells.1 The function of this small phosphate molecule in the erythrocyte remained a mystery, however, until we demonstrated over 40 years later that it is a powerful regulator of the oxygen affinity of hemoglobin.2 It was further shown that it acts by complexing hemoglobin in the deoxygenated state, a reaction that inhibits oxygen binding but facilitates its unloading at physiologic oxygen tensions.3 DPG thus functions as an essential cofactor of the oxygen carrier. Since the affinity of hemoglobin for oxygen and the organic phosphate is reciprocal, this mechanism . . .
The Epidemiologic Necropsy
Authors: P. D. Sullivan
Journal: JAMA (1987)

<h3>To the Editor.—</h3> McFarlane et al,<sup>1</sup>in the July 17, 1987,<i>JAMA</i>article entitled "The `Epidemiologic Necropsy,' " address the question of the extent of the hypothetical "undetected reservoir" of lung cancer by a retrospective analysis of the autopsy findings at a Connecticut hospital for a recent ten-year period (1972 to 1981) and compare their results with the incidence rates derived from cases reported to the Connecticut Tumor Registry. The authors compute age- and sex-standardized occurrence rates that are greater by a factor of 10 (3.95 men and 14.86 women) than the rates from the Connecticut Tumor Registry. However, in computing the two sets of rates, the authors make two errors. First, there seems to be a computational inaccuracy. The authors, in obtaining the crude Connecticut Tumor Registry rates, divide by the 1970 to 1979 population of Connecticut aged 20 years and older but base the age-adjusted rates on the
The Changing Neurourologic Lesion in Myelodysplasia
Authors: Michael R. Spindel
Journal: JAMA (1987)

Seventy-nine newborns with myelodysplasia were followed up for 1 1/2 to six years with serial roentgenographic, neurologic, and urodynamic evaluations. Twenty-nine infants (37%) demonstrated changes in external urethral sphincter innervation during the first three years of life. Of the group who changed, 896% (25/29 infants) did so in the first year, 10% (3/29 infants) in the second year, and 4% (1/29 infants) in the third. The risk factor for change was 32%, 6%, and 2%, respectively, during each of these three years. Fifteen infants (19% of the total) experienced neurourologic deterioration while 14 infants (18%) improved. Seven newborns underwent a second neurosurgical procedure resulting in improvement in four, stabilization in two, and further deterioration in one. These findings underline the importance of early and continued neurologic and urologic surveillance in children with myelodysplasia because it is a dynamic disease process.
Preactivated thiomers as mucoadhesive polymers for drug delivery
Authors: Javed Iqbal, Gul Shahnaz, Sarah Dünnhaupt, Christiane Müller, Fabian Hintzen, Andreas Bernkop-Schnürch
Journal: Biomaterials (2011)

This study was aimed to synthesize polymeric excipients with improved mucoadhesive, cohesive and in situ-gelling properties to assure a prolonged retention time of dosage forms at a given target site, thereby achieving an increased uptake and improved oral bioavailability of certain challenging therapeutic agents such as peptides and proteins. Accordingly, poly(acrylic acid)-cysteine-2-mercaptonicotinic acid (PAA-cys-2MNA) conjugates were synthesized by the oxidative S-S coupling of PAA-cys (100-, 250- and 450 kDa) with 2-mercaptonicotinic acid (2MNA). Unmodified PAAs, PAAs-cys (thiomers) and PAA-cys-2MNA (100-, 250- and 450 kDa) conjugates were compressed into tablets to perform disintegration tests, mucoadhesion studies and rheological measurements. Moreover, cytotoxicty of the polymers was determined using Caco-2 cells. The resulting PAA-cys-2MNA (100-, 250- and 450 kDa) conjugates displayed 113.5 ± 12.7, 122.7 ± 12.2 and 117.3 ± 4.6 μmol/g of 2-mercaptonicotinic acid, respectively. Due to the immobilization of 2MNA, the PAA-cys-2MNA (pre-activated thiomers) conjugates exhibit comparatively higher swelling properties and disintegration time to the corresponding unmodified and thiolated polymers. On the rotating cylinder, tablets based on PAA-cys-2MNA (100-, 250- and 450 kDa) conjugates displayed 5.0-, 5.4- and 960-fold improved mucoadhesion time in comparison to the corresponding unmodified PAAs. Results achieved from tensile studies were found in good agreement with the results obtained by rotating cylinder method. The apparent viscosity of PAA-cys-2MNA (100-, 250- and 450 kDa) conjugates was improved 1.6-, 2.5- and 206.2-fold, respectively, in comparison to the corresponding unmodified PAAs. Moreover, pre-activated thiomers/mucin mixtures showed a time dependent increase in viscosity up to 24 h, leading to 7.0-, 18.9- and 2678-fold increased viscosity in comparison to unmodified PAAs (100-, 250- and 450 kDa), respectively. All polymers were found non-toxic over Caco-2 cells. Thus, on the basis of achieved results the pre-activated thiomers seem to represent a promising generation of mucoadhesive polymers which are safe to use for prolonged residence time of drug delivery systems to target various mucosa.
Abstract 1736: Src inhibitor dasatinib enhances anti-tumor activity of irreversible or T790M-selective epidermal growth factor receptor-tyrosine kinase inhibitors in non-small cell lung cancer cells with T790M gate-keeper mutation
Authors: Takeshi Yoshida, Guolin Zhang, Yun Bai, Arthur Edwards, Bin Fang, Bhupendra Rawal, Takafumi Okabe, Isamu Okamoto, Kazuhiko Nakagawa, Eric B. Haura
Journal: Cancer Research (2011)

Abstract Despite the therapeutic benefit of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with EGFR mutation, most if not all eventually develop resistance to these drugs. A secondary mutation of EGFR (T790M) accounts for 50% of all cases of acquired resistance to EGFR-TKIs. Although irreversible EGFR-TKIs are thought to be one of the strategies to overcome T790M, the efficacy of these drugs appears limited. To investigate how signal transduction is altered in NSCLC cells with T790M, we generated PC9GR cells with T790M by long term gefitinib exposure of PC9 cells with exon 19 deletion. Global phospho-proteomics approach revealed that Src family kinases were phosphorylated by erlotinib treatment in PC9GR cells, suggesting that Src family kinases compensate EGFR inhibition in NSCLC cells with T790M. Western blot assays demonstrated that BIBW2992, an irreversible EGFR-TKI currently in several clinical trials, also activated Src family kinases in PC9GR and H1975 NSCLC cells with T790M. The Src inhibitor dasatinib combined with BIBW2992 abolished this Src phosphorylation along with complete suppression of phospho Akt and Erk. In addition, significant PARP cleavage was observed in these cells suggesting apoptotic cell death. Consistent with the effects on cell signaling and apoptosis, dasatinib enhances anti-tumor activity of BIBW2992 in both GLO cell proliferation assay and caspase-3 apoptosis assay in PC9GR and H1975 cells. Additional experiments also demonstrated that dasatinib enhanced the effects of T790M selective EGFR-TKI WZ4002, which was recently reported to be another possible strategy to overcome T790M, in PC9GR and H1975 cells. Finally, the combination of BIBW2992 and dasatinib showed significant in vivo tumor suppression (including tumor regression) in PC9GR xenograft studies. These results suggest a role for Src in maintaining downstream signaling despite irreversible EGFR inhibitors and support further studies of irreversible EGFR combined with dasatinib in NSCLC patients who acquired resistance to EGFR-TKI by T790M. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1736. doi:10.1158/1538-7445.AM2011-1736
A New Look at Clinical Privileges for Procedures
Authors: EUGENE A. HILDRETH
Journal: Annals of Internal Medicine (1987)

Editorials1 October 1987A New Look at Clinical Privileges for ProceduresEUGENE A. HILDRETH, M.D.EUGENE A. HILDRETH, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-107-4-585 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn preparing guidelines for clinical competence in specific medical procedures, the American College of Physicians (ACP) intends to suggest minimum criteria necessary for competent performance of the procedures. It is hoped the guidelines will be useful in education and evaluation, but especially during the course of privilege delineation decisions.In addressing the questions of why the ACP has begun such action, a number of influencing factors should be recognized. Members of the ACP have asked the College to address the issues of credentialing procedures in order to assist them in their individual institutions. Credentialing is critical to the practice of... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Reading Hospital and Medical Center Reading, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByAssessment of a Bronchoscopy SimulatorTraining Internists in Procedural SkillsRobert S. Wigton, MDThe procedural and interpretive skills that third-year medicine clerks should masterThe gastroenterologist: physician or technician?Procedural Skills of Practicing Gastroenterologists A National Survey of 700 Members of the American College of PhysiciansRobert S. Wigton, MD, Linda L. Blank, BA, Howard Monsour, MD, Jo A. Nicolas, BAProcedural Skills of Practicing Nephrologists A National Survey of 700 Members of the American College of PhysiciansThomas G. Tape, MD, Robert S. Wigton, MD, Linda L. Blank, BA, Jo A. Nicolas, BAProcedural Skills of the General Internist A Survey of 2500 PhysiciansRobert S. Wigton, MD, Jo A. Nicolas, BA, Linda L. Blank, BAProcedural Skills Training in Internal Medicine Residencies A Survey of Program DirectorsRobert S. Wigton, MD, Linda L. Blank, BA, Jo A. Nicolas, BA, Thomas G. Tape, MDRemarks from the organizational representatives Medical quality assessment and the american college of physiciansEvaluating internists’ clinical competence 1 October 1987Volume 107, Issue 4Page: 585-587 Issue Published: 1 October 1987 PDF DownloadLoading ...
Erratum: “Identification and molecular characterization of the <sup>–CAMPANIA</sup> deletion, a novel α°‐thalassemic defect, in two unrelated Italian families” by Sessa et al., <i>Am J Hematol</i> 2010, DOI number 21591
Authors: Raffaele Sessa, Stella Puzone, Massimiliano Ammirabile, Carmelo Piscopo, Leonilde Pagano, Simona Colucci, Paola Izzo, Michela Grosso
Journal: American Journal of Hematology (2010)

An error was made in the title of the above-mentioned publication. The degree symbol in the term α°-thalassemic is incorrect and should be a zero. The correct article title appears below: “Identification and molecular characterization of the –CAMPANIA deletion, a novel α0-thalassemic defect, in two unrelated Italian families” We apologize to readers for any confusion.
Elevated C-reactive protein predicts pulmonary vein narrowing following pulmonary vein ablation of atrial fibrillation
Authors: Mohammad Alghoul, Nassir F. Marrouche, David O. Martin, Robert Schweikert, Walid Saliba, Raed H. Abdelhadi, Alejandro Perez-Lugones, Ahmad Abdul-Karim, Oussama Wazni, Andrea Natale
Journal: Journal of the American College of Cardiology (2003)
Children of Choice: Freedom and the New Reproductive Technologies
Authors: Fredrick R. Abrams
Journal: JAMA (1994)

This book is a valuable boost to the perpetual effort of society to overtake and accommodate new technology, specifically that affecting reproduction. Professor Robertson has produced in his characteristic way a well-referenced evaluation that is consistent and coherent although not without controversy. The analysis subjects seven technical interventions to scrutiny through the "lens of procreative liberty." Robertson is the first to admit that the majority of reproduction will continue in the accustomed way, but he notes that an irrevocable change has occurred in the nature of human reproduction. Technology continually adds to choice in whether (and when) to procreate, continue a pregnancy after conception, attempt to overcome infertility, widen the collaborative character of reproduction beyond the traditional father and mother couple, genetically shape offspring (and how far to go to prevent harm to those in utero), and use reproductive capacity for nonreproductive purposes such as fetal tissue transplantation. He asserts
COMPARATIVE STUDIES IN ROUS SARCOMA WITH VIRUS, TUMOR CELLS, AND CHICK EMBRYO CELLS TRANSFORMED IN VITRO BY VIRUS
Authors: Robert M. Dougherty, Herbert R. Morgan
Journal: The Journal of Experimental Medicine (1962)

Chick embryo fibroblasts infected in vitro with Rous sarcoma virus have properties similar to tumor cells when injected into virus-immune chickens. When such virus-transformed fibroblasts are injected into normal chickens, they apparently participate in the production of tumors independent of their release of virus and are thus apparently malignant in vivo.
Time for evidence based medical education
Authors: S. Petersen
Journal: BMJ (1999)

Education and debate pp 1265−83

No doctor will deny the need for evidence based clinical practice, and all responsible professionals try to keep up with research in their discipline.1 For many, however, the education of the next generation of doctors is also a major responsibility, yet the same professional standards are not so commonly applied. All doctors have been successful medical students, and it seems easy to assume that this alone qualifies them to educate others. Few surgeons would claim that surviving a surgical procedure qualifies a patient to perform it on another, yet how often do we hear, “There was none of this gobbledegook in my day, yet I learnt medicine well. I know about medical education. I'm not going to change.” Why do these attitudes persist? What are the barriers to effective, evidence based medical education, and how may they be overcome?

It is hard for clinical teachers to learn about medical education research, partly because there …
Mortality and morbidity after hip fractures.
Authors: G S Keene, M J Parker, G A Pryor
Journal: BMJ (1993)

To study the mortality and morbidity associated with proximal femoral fractures with reference to fracture type (intracapsular and extracapsular).Consecutive prospective study with 12 month follow ups.Two British trauma receiving centres.1000 consecutive acute proximal femoral fractures (fractured necks of femur) in 972 patients.Significantly higher mortality at one year was seen in patients with extracapsular fractures (188/490; 38%) than in those with intracapsular fractures (147/510; 29%; p < 0.01). Greater morbidity was experienced during the study period by patients with extracapsular fractures, who were less mobile and less independent at the time of their injury.The rise in average age of presentation with proximal femoral fracture is associated with a persistently high mortality (33%) and morbidity, greater in patients with an extracapsular fracture. Comparison with other studies, principally from outside Britain, is difficult, but despite advancing standards of care the mortality and morbidity of femoral neck fractures remains high, placing an ever increasing burden on the health service.
Endoscopic Fistulotomy (EFT) for Parapapillary Choledochoduodenal Fistula
Authors: Y. Urakami, S. Kishi
Journal: Endoscopy (1978)

Up to now, surgery was the only possible treatment for choledochoduodenal fistulas, which are seen more often in Japan than in Europe. This paper presents the value and effect of endoscopic fistulotomy (EFT) as an alternative treatment in those cases. Parapapillary choledochoduodenal fistulas are abserved usually on the longitudinal fold of the papilla or on its oral side. The papillotome is inserted into the common bile duct through the orifice of the duodenal papilla, then the wall between its orifice and the fistula is cut to open widely the distal portion of the choledochus. EFT was performed successfully in 7 cases. The procedure led to a wide open stoma of the distal common bile duct with free bile outflow. Residual stones, a common occurrence in cases of parapapillary choledochoduodenal fistulas, may pass spontaneously after EFT or can be removed with a basket catheter. In cases of parapapillary choledochoduodenal fistula, EFT is a reliable method, especially in high-risk patients, and an alternative to surgical treatment.
Paroxysmal Nocturnal Dyspnoea
Authors: E. Montuschi
Journal: BMJ (1965)

Natural Hepatotoxins SIR,-The juxtaposition of your recent leading article (15 May, p. 1261) on natural hepatotoxins with that on communication difficulties inherent in the increasing proliferation of specialist journals (" Too Many Words," p. 1264) was timely.For the ques- tion, " Are these toxins in any part responsible for the chronic liver disease which is so wide-
Cytomegalovirus pp65 limits dissemination but is dispensable for persistence
Authors: Daniel Malouli, Scott G. Hansen, Ernesto S. Nakayasu, Emily E. Marshall, Colette M. Hughes, Abigail B. Ventura, Roxanne M. Gilbride, Matthew S. Lewis, Guangwu Xu, Craig Kreklywich, Nathan Whizin, Miranda Fischer, Alfred W. Legasse, Kasinath Viswanathan, Don Siess, David G. Camp, Michael K. Axthelm, Christoph Kahl, Victor R. DeFilippis, Richard D. Smith, Daniel N. Streblow, Louis J. Picker, Klaus Früh
Journal: Journal of Clinical Investigation (2014)

The most abundantly produced virion protein in human cytomegalovirus (HCMV) is the immunodominant phosphoprotein 65 (pp65), which is frequently included in CMV vaccines. Although it is nonessential for in vitro CMV growth, pp65 displays immunomodulatory functions that support a potential role in primary and/or persistent infection. To determine the contribution of pp65 to CMV infection and immunity, we generated a rhesus CMV lacking both pp65 orthologs (RhCMVΔpp65ab). While deletion of pp65ab slightly reduced growth in vitro and increased defective particle formation, the protein composition of secreted virions was largely unchanged. Interestingly, pp65 was not required for primary and persistent infection in animals. Immune responses induced by RhCMVΔpp65ab did not prevent reinfection with rhesus CMV; however, reinfection with RhCMVΔUS2-11, which lacks viral-encoded MHC-I antigen presentation inhibitors, was prevented. Unexpectedly, induction of pp65b-specific T cells alone did not protect against RhCMVΔUS2-11 challenge, suggesting that T cells targeting multiple CMV antigens are required for protection. However, pp65-specific immunity was crucial for controlling viral dissemination during primary infection, as indicated by the marked increase of RhCMVΔpp65ab genome copies in CMV-naive, but not CMV-immune, animals. Our data provide rationale for inclusion of pp65 into CMV vaccines but also demonstrate that pp65-induced T cell responses alone do not recapitulate the protective effect of natural infection.