tbuckley/cabot-search huggingface dataset:
Abstract IA5: Translating genetic discoveries to patient care
Authors: Ralph H. Hruban
Journal: Cancer Research (2015)

Abstract Next-generation sequencing technologies have changed the speed at which cancer genetics research can be performed and this research has fundamentally changed our understanding of pancreatic cancer. 1. Families: It has been estimated that 10% of pancreatic cancer has an inherited basis. Whole-exome and whole-genome sequencing studies have led to the discovery of several new familial pancreatic cancer genes including PALB2 and ATM. It is hoped that new multi-institutional collaborative efforts will dramatically increase the pace of discovery. Patients found to harbor a genetic alteration that predisposes them to pancreatic cancer will be the first to benefit from early detection efforts. 2. Cystic neoplasms: Some cystic lesions in the pancreas are harmless benign tumors, while others are precancerous. Lives can be saved if significant precursor lesions can be identified and removed, but there is a risk of over-treatment if the benign harmless cysts are removed. Whole-exome sequencing all of the four major types of cystic neoplasms of the pancreas has revealed a pattern of mutations specific for each cyst type. In the future, cyst fluid can be sampled and cyst type determined by sequencing. 3. Early detection: The genetic alterations in a cancer and in its precursor lesions offer extremely sensitive and highly specific markers for the early detection of pancreatic neoplasia. These genetic alterations can be detected in pancreatic juice collected at endoscopy and even in the plasma. 4. Invasive cancer: Genetic alterations in a cancer can be the basis for individualized therapies. 5. Metastatic cancer: The sequencing of metastatic cancer has helped define the timeline of tumor progression in the pancreas. In sum, and in short, these are exciting times in the war against pancreatic cancer. The translation of discoveries made by sequencing pancreatic tumors to patient care holds the promise for reducing mortality from this terrible disease. Citation Format: Ralph H. Hruban. Translating genetic discoveries to patient care. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr IA5.
Abstract 17664: Role of miR-92a for Endothelial Cell Function and Reendothelialization Following Vascular Injury
Authors: Daniel Sedding, Jan-Marcus Daniel, Wiebke Bielenberg, Angelika Bonauer, Eva van Rooij, Stefanie Dimmeler
Journal: Circulation (2010)

Background: MicroRNAs (miR) are small noncoding RNAs that regulate gene expression by binding to the cellular transcript leading to translational repression or degradation of the target mRNA. So fa...
A randomized trial comparing the dorzolamide-timolol combination given twice daily to monotherapy with timolol and dorzolamide11Ms. Boyle, Dr. Ghosh, and Dr. Adamsons were employees of Merck &amp; Co., Inc, the manufacturer of timolol and dorzolamide, at the time this study was conducted. COSOPT and TRUSOPT are trademark products of Merck &amp; Co., Inc, Whitehouse Station, New Jersey. The other authors have no proprietary interest in timolol, dorzolamide, or Merck.
Authors: Janet E Boyle, Kalyan Ghosh, David K Gieser, Ingrid A Adamsons
Journal: Ophthalmology (1998)
Bipolar affective disorder---left out in the cold
Authors: R. Morriss, M. Marshall, A. Harris
Journal: BMJ (2002)

The national strategic framework for mental health states that “one person in 250 will have a psychotic illness such as schizophrenia or bipolar affective disorder.” It goes on to cite bipolar affective disorder as one of the 10 leading causes of disability worldwide in adults aged 15-44.1 How surprising then that the service needs of people with bipolar affective disorder receive no specific consideration in this major policy document.

There are four reasons why the national service framework should have given special consideration to the needs of people with bipolar affective disorder. Firstly, most patients with bipolar affective disorder have the potential, with optimal treatment, to return to normal function and contribute to the economy. With suboptimal treatment, however, many will have a poor long term outcome and needlessly become a burden to families and society.2 Yet there is evidence that treatment is generally suboptimal. For example, a survey (n=1004) of members of the Manic Depression Fellowship, a British organisation for people with bipolar affective disorder, found that only 19% were in full time work, although 40% were graduates and 69% wanted to work.3 Longitudinal observational …
Characteristics of Clinical Studies Conducted Over the Total Product Life Cycle of High-Risk Therapeutic Medical Devices Receiving FDA Premarket Approval in 2010 and 2011
Authors: Vinay K. Rathi, Harlan M. Krumholz, Frederick A. Masoudi, Joseph S. Ross
Journal: JAMA (2015)

<h3>Importance</h3> The US Food and Drug Administration (FDA) approves high-risk medical devices, those that support or sustain human life or present potential unreasonable risk to patients, via the Premarket Approval (PMA) pathway. The generation of clinical evidence to understand device safety and effectiveness is shifting from predominantly premarket to continual study throughout the total product life cycle. <h3>Objective</h3> To characterize the clinical evidence generated for high-risk therapeutic devices over the total product life cycle. <h3>Design and Setting</h3> All clinical studies of high-risk therapeutic devices receiving initial market approval via the PMA pathway in 2010 and 2011 identified through ClinicalTrials.gov and publicly available FDA documents as of October 2014. <h3>Main Outcomes and Measures</h3> Studies were characterized by type (pivotal, studies that served as the basis of FDA approval; FDA-required postapproval studies [PAS]; or manufacturer/investigator-initiated); premarket or postmarket; status (completed, ongoing, or terminated/unknown); and design features, including enrollment, comparator, and longest duration of primary effectiveness end point follow-up. <h3>Results</h3> In 2010 and 2011, 28 high-risk therapeutic devices received initial marketing approval via the PMA pathway. We identified 286 clinical studies of these devices: 82 (28.7%) premarket and 204 (71.3%) postmarket, among which there were 52 (18.2%) nonpivotal premarket studies, 30 (10.5%) pivotal premarket studies, 33 (11.5%) FDA-required PAS, and 171 (59.8%) manufacturer/investigator-initiated postmarket studies. Six of 33 (18.2%) PAS and 20 of 171 (11.7%) manufacturer/investigator-initiated postmarket studies were reported as completed. No postmarket studies were identified for 5 (17.9%) devices; 3 or fewer were identified for 13 (46.4%) devices overall. Median enrollment was 65 patients (interquartile range [IQR], 25-111), 241 patients (IQR, 147-415), 222 patients (IQR, 119-640), and 250 patients (IQR, 60-800) for nonpivotal premarket, pivotal, FDA-required PAS, and manufacturer/investigator-initiated postmarket studies, respectively. Approximately half of all studies used no comparator (pivotal: 13/30 [43.3%]; completed postmarket: 16/26 [61.5%]; ongoing postmarket: 70/153 [45.8%]). Median duration of primary effectiveness end point follow-up was 3.0 months (IQR, 3.0-12.0), 9.0 months (IQR, 0.3-12.0), and 12.0 months (IQR, 7.0-24.0) for pivotal, completed postmarket, and ongoing postmarket studies, respectively. <h3>Conclusions and Relevance</h3> Among high-risk therapeutic devices approved via the FDA PMA pathway, total product life cycle evidence generation varied in both the number and quality of premarket and postmarket studies, with approximately 13% of initiated postmarket studies completed between 3 and 5 years after FDA approval.
Erratum: Corrigendum: AP2γ regulates basal progenitor fate in a region- and layer-specific manner in the developing cortex
Authors: Luisa Pinto, Daniela Drechsel, Marie-Theres Schmid, Jovica Ninkovic, Martin Irmler, Monika S Brill, Laura Restani, Laura Gianfranceschi, Chiara Cerri, Susanne N Weber, Victor Tarabykin, Kristin Baer, François Guillemot, Johannes Beckers, Nada Zecevic, Colette Dehay, Matteo Caleo, Hubert Schorle, Magdalena Götz
Journal: Nature Neuroscience (2010)
Health Officials Brace for Flu Season
Authors: Mike Mitka
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Hematologic outcomes of MDS treatment with hypomethylating agents in community practice.
Authors: R. Bordoni, B. A. Feinberg, J. W. Gilmore, S. Haislip, E. Kim, J. Jackson, E. Farrelly, D. Buchner
Journal: Journal of Clinical Oncology (2010)

6601 Background: Hypomethylating agents (HMAs) treat myelodysplastic syndromes (MDS) through suppression of abnormal clones may cause low hemoglobin (Hgb), platelet (PLT) deficiencies, and reduced absolute neutrophil count (ANC). The purpose of this study was to examine hematologic outcomes in MDS among patients treated with HMAs in a large community hematology/oncology practice. Methods: In a retrospective observational study using electronic medical record data, patients with an ICD-9 diagnosis of MDS from June 1 2006 to May 31 2009 who received at least 1 cycle of a single HMA (decitabine [DAC] or azacitidine [AZA], 5-day IV dosing for each treatment) with pretreatment and end of treatment Hgb, PLT count, and ANC were included. Multivariate logistic regression assessed predictors of end of treatment response (Hgb ≥ 11g/dL without transfusion or erythrocyte stimulating agent; PLT ≥ 100 K cells/μL without transfusion; ANC ≥ 1,000 cells/mm3 without colony stimulating factors) adjusting for baseline lab values, age, gender, co-morbidities, and growth factor use during treatment. HMA choice was also studied as a predictor of outcome. Results: A total of 137 patients (mean age 72.2; 57% male) met full inclusion criteria (DAC = 84, AZA = 53). Sample baseline mean values were Hgb = 9.7 g/dL; PLT = 107K cells/μL; ANC = 2,240 cells/mm3. Mean number of cycles was 4 (range 1- 16) for DAC and 5 (range 1-23) for AZA. Total number of cycles significantly predicted Hgb, PLT and ANC response (OR 1.19, p = 0.029; OR 1.15, p = 0.031; OR 1.16, p = 0.047). There was a trend toward a greater likelihood of Hgb ≥ 11g/dL for DAC vs. AZA (OR 2.70, p = 0.085). Growth factor use during treatment was negatively associated with Hgb and ANC response (OR 0.85, p = 0.007; OR 0.96, p = 0.046). There was no difference between treatments in likelihood of PLT or ANC response. Conclusions: Patients treated with HMAs for MDS are more likely to achieve hematologic response when treated with a greater number of cycles. DAC may be associated with a greater likelihood of erythroid response compared with AZA. This variance from trial-based data may be due to the use of the 5-day IV dosing regimen for AZA. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai Eisai Eisai
Cardiac Tamponade in Systemic Lupus Erythematosus
Authors: PK Nigam, IM Sethi, SR Gupta
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A temporal analysis of the central neural processing of itch
Authors: C.E. Kleyn, S. McKie, A. Ross, R. Elliott, C.E.M. Griffiths
Journal: British Journal of Dermatology (2012)

Pruritus, or itch, is the most prevalent symptom of allergic and inflammatory skin disease. Although it is known that itch induces activation of a neural network in the brain, the temporal dynamics of the network as well as the pathophysiology and neurobiology are not well understood.The study aimed to elucidate (i) the temporal dynamics of the itch response identified in earlier studies and (ii) the relationship between central and subjective responses to itch.Using a novel time-series analysis, we performed a double-blind, placebo-controlled, randomized, within-subject functional magnetic resonance imaging (fMRI) study of the cerebral processing of histamine-induced itch in healthy volunteers (n = 16) by tracking the 8-min period following a single skin prick.Histamine-induced itch compared with saline resulted in significant area under the curve blood oxygen level dependent (BOLD) signal changes in the middle/superior temporal gyrus and right inferior frontal gyrus/insula. We observed negative itch-induced BOLD signal changes compared with saline in (i) the pregenual anterior cingulate cortex (ACC)/medial frontal gyrus, (ii) subgenual ACC/ventral striatum, (iii) bilateral temporal pole/parahippocampal gyrus and (iv) several regions within the cerebellum. We noted a trend significance in the left precentral gyrus part of the motor cortex. The BOLD signal change in several of these regions correlated with perception of itch intensity.In contrast to other fMRI studies we observed a multifocal negative signal. An improved understanding of both activated and deactivated brain regions during the itch response may in the long term facilitate development of more effective management strategies.
Images of war: the other side
Authors: Syed M H Rizvi, Kamyar M Hedayat, Asad J Raja, Jerome A Singh, Tania L DePellegrin
Journal: BMJ (2003)

Following are edited excerpts from the Rapid Responses generated by this article, which can be read in their entirety at http://bmj.com/cgi/eletters/326/7393/774
Diabetes Mellitus: A Further Study of the Etiology of the Disease
Authors: John C. Krantz
Journal: Annals of Internal Medicine (1929)

Article1 May 1929Diabetes Mellitus: A Further Study of the Etiology of the DiseaseJOHN C. KRANTZ JR.JOHN C. KRANTZ JR.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-2-11-1209 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIntroductionRecent literature indicates the existence of a hyperglycemic principle in the blood of diabetic animals. Thus L. Kepinov and S. Petit-Dutailis (1) showed the existence of a principle in diabetic blood which acts antagonistically to the action of insulin. These investigators depancreatized dogs to the extent that a normal blood sugar was just maintained: in these dogs the injection of large quantities of diabetic blood produced a hyperglycemia which lasted for several days. Depisch and Hasenohrl (2) found the serum from a case of diabetes with a paranephritic abscess to have an insulin-inhibiting action on rabbits. Serum from cases...(1) KEPINOVPETIT-DUTAILIS LS: Comptes Rendue de la Soc. Biol. (1927) t. XCVII, p. 1597 and (1928) t. XCVIII, p. 425 and 1193. Google Scholar(2) DEPISCHHASENŐHRL : Z. ges. exptl. Med. 58, (1927) 110, through C. A. 22 (1928) 2782. CrossrefGoogle Scholar(3) BERGEY GH: Proc. Soc. Exptl. Biol. and Med. 24 (1926) 229. CrossrefGoogle Scholar(4) SCHULTZ EW: Proc. Soc. Exp. Biol. and Med. 25 (1928) 432. CrossrefGoogle Scholar(5) ETTINGERREED GHGB: Jour. Inf. Diseases 43 (1928) 399. CrossrefGoogle Scholar(6) MACHTLIVINGSTON : Journ. Gen. Phys. 4 (1922) 573. CrossrefMedlineGoogle Scholar(7) MACHTKRANTZ : Journ. Pharm. and Exptl. Therap. 31 (1927) 11. Google Scholar(8) MACHTKRANTZ : Journ. Am. Pharm. Ass'n. 16 (1927) 210. Google Scholar(9) SHAFFERHARTMANN : Journ. Biol. Chem. 45 (1921) 349. CrossrefGoogle Scholar(10) MACHTROWE : Proc. Soc. Exptl. Phys. 24 (1926) 649. CrossrefGoogle Scholar(11) SHIVE JW: Physiol. Researches (1915) 1,327. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Baltimore, Md.*From the Laboratory of Pharmaceutical Research, Sharp and Dohme, Baltimore, Md. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1929Volume 2, Issue 11Page: 1209-1215KeywordsAbscessesBloodBlood sugarDiabetes mellitusDrug research and developmentEtiologyHyperglycemiaInsulinRabbitsResearch laboratories ePublished: 1 December 2008 Issue Published: 1 May 1929 PDF downloadLoading ...
Ernährung und Stoffwechselkrankheiten.
Authors: Friedrich Umber
Journal: JAMA (1926)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 13917: Inhibition of GRK2 Prevents Cardiac Fibroblast-Mediated Maladaptive Ventricular Remodeling
Authors: Jennifer L Philip, Xianyao Xu, Mei Han, Jinju Li, Abdur Razzaque, Shahab A Akhter
Journal: Circulation (2014)

Remote (non-infarct) territory fibrosis is a significant cause of post-myocardial infarction (MI) heart failure (HF). We have previously shown that increased activity of G protein-coupled receptor kinase-2 (GRK2) in adult human cardiac fibroblasts (CF) isolated from failing hearts is an important mechanism of cardiac fibrosis. This study investigates the potential therapeutic role of GRK2 inhibition on CF biology in vivo. Adult male rats underwent LAD ligation to induce post-MI HF. GRK2 was inhibited by intra-coronary adenoviral-mediated delivery of a GRK2 inhibitor (Ad-GRK2ct) immediately following LAD ligation (n=11). Control rats received a null adenovirus (n=10). Animals were studied prior to and up to 12 weeks (wks) post-MI and adenoviral delivery. There was a significant decline in LV function at 2 wks post-MI which was present through 12 wks [Fractional shortening: 0.35±0.01 vs. 0.52±0.01, p&lt;0.01] in Ad-null rats vs. pre-MI. Remote territory (non-infarct area) fibrosis increased by 2 wks post-MI [6±1% vs. 2±1% fibrosis, p&lt;0.01] progressing by 12 wks to 12% fibrosis [p&lt;0.01], consistent with adverse remodeling. Collagen synthesis was upregulated 2.9-fold in CF isolated 12 wks post-MI [p&lt;0.03] and GRK2 activity was increased 1.4-fold [p=0.002]. There was a 42% decrease in intracellular cAMP [p&lt;0.05] and loss of β-agonist-stimulated inhibition of collagen synthesis characteristic of normal CF [3969±1058 vs. 708±95 cmp/mg protein, p&lt;0.01]. Intra-coronary delivery of Ad-GRK2ct following LAD ligation significantly inhibited post-MI LV dysfunction vs. Ad-Null as measured by improved fractional shortening [0.42±0.01 vs. 0.30±0.02, p&lt;0.01] and ejection fraction [72±1% vs. 57±2%, p&lt;0.01]. Ad-GRK2ct also decreased peri-infarct and remote territory fibrosis by 60% [p&lt;0.001]. Consistent with these findings, Ad-GRK2ct resulted in decreased a-SMA, collagen I, and collegen III expression in CF isolated 12 wks post-MI vs. Ad-Null providing evidence of decreased post-MI CF activation and myofibroblast transformation with Ad-GRK2ct. Targeted inhibition of GRK2 and restoration of β-adrenergic signaling/cAMP production in CF may represent a novel therapeutic approach to prevent pathological fibrosis and maladaptive remodeling post-MI.