tbuckley/cabot-search huggingface dataset:
Abstract 20425: Metabolic Burden Switches Impact of Betatrophin (ANGPTL8) R59W Mutation From Atheroprotective to Atherogenic Lipid Profiles
Authors: Atsushi Nohara, Kunimasa Yagi, Jianhui Liu, Azusa Ohbatake, Satoko Okazaki, Mie Yoshida, Mika Mori, Chiaki Nakanishi, Hayato Tada, Masa-aki Kawashiri, Akihiro Inazu, Masakazu Yamagishi, Hiroshi Mabuchi
Journal: Circulation (2014)

Betatrophin (ANGPTL8) is recently identified pancreatic s cell proliferating hormone, but also known as lipoprotein-lipase (LPL) inhibitor. Loss-of-function variant R59W is common among Hispanic and African-Americans compared with European-Americans. Insulin, obesity, feeding, and lypolytic-stimuli can regulate betatrophin expression, and impact of this variant may vary dependent on metabolic burden.   Methods:  A total of 251 patients (Male 131, Age 58 ± 14 ys) with dyslipidemia, and 275 general healthy control subjects from same residential area of Japan were investigated. Fasting lipid profiles by ultracentrifugation and post-heparin lipoprotein lipase activities (PHLA) without lipid lowering drugs, 75gOGTT were evaluated. Coronary stenosis index (CSI) with angiography was evaluated in 162 patients.   Results:  R59W minor allele frequency was 25% in general population and 40% in dyslipidemic patients. In general population, WW homozygotes showed significantly low TG (89 ± 31 vs. 144 ± 94 mg/dL,  p  p  p  p  p  p  p  p  p  p  p    Conclusion:  Betatrophin R59W variant may be beneficial for healthy group, but was worsening genetic contributor of metabolic disorder in presence of metabolic burden especially low LPL activity.
Colonic Changes in Chronic Arthritis
Authors: W. H. Dickson
Journal: Annals of Internal Medicine (1931)

Article1 October 1931Colonic Changes in Chronic ArthritisW. H. DICKSON, M.D., C.M., F.R.C.P.W. H. DICKSON, M.D., C.M., F.R.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-5-4-408 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe etiology and progress of changes in the colon so often noted in arthritis have been very great controversial points. Where many different opinions are held as to the cause of a condition and many methods of treatment advanced for the alleviation of the disease, it is evident a true understanding of the basic factors has not been reached. The roentgenological observations which we report here were noted on examination of patients suffering with chronic arthritis. The investigation was carried out by the permission of Professor Duncan Graham, and with the collaboration of Dr. A. A. Fletcher of the Department...Bibliography1 GOLDTHWAITEBROWN JELT: The cause of gastroptosis and enteroptosis with their possible importance as a causative factor in the rheumatoid diseases, Boston Med. and Surg. Jr., 1910, clxii, 695-703. CrossrefGoogle Scholar2 LANE A: Chronic intestinal stasis Surg. Gynec. Obst., 1910, xl, 495-500. Google Scholar3 BASSLER A: Discussion of the surgical theories of intestinal stasis, Jr. Am. Med. Assoc., 1914, lxiii, 1469-1473. CrossrefGoogle Scholar4 DANIEL P: Septic infection versus chronic intestinal stasis; The legality of ileo-colostomy for arthritis, Clin. Jr., 1913, xli, 305 320. Google Scholar5 KEITH A: A new theory of the causation of enterostasis, Lancet, 1915, ii, 371-375. CrossrefGoogle Scholar6 JORDAN AC: Radiography in intestinal stasis, Lancet, 1911, ii, 1824-1828. A discussion on alimentary toxemia; its sources, consequences and treatment, Proc. Roy. Soc. of Med., 1913, vi, 311-315. CrossrefGoogle Scholar7 SMITH R: Relation of surgical pathology of right lower quadrant to arthritis, Jr. Bone and Joint Surg., 1928, x, 57-61. Google Scholar8 TAYLOR RG: Surgical lesions of right lower quadrant, demonstrated in patients with chronic deforming arthritis by x-ray opaque meal examinations, Jr. Bone and Joint Surg., 1928, x, 62-68. Google Scholar9 PEMBERTON R: The metabolism and treatment of rheumatoid arthritis, Am. Jr. Med. Sci., 1917, cliii, 678-692. CrossrefGoogle Scholar10 FLETCHER AA: Chronic arthritis, Canad. Med. Assoc. Jr., 1922, xii, 633-637. Google Scholar11 MCGARRISON R: Studies in deficiency diseases, Oxford University Press, London, 1921. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: (Can.), Toronto*Read at the Baltimore Meeting of the American College of Physicians, March 27, 1931. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1931Volume 5, Issue 4Page: 408-416KeywordsArthritisColonEtiology ePublished: 1 December 2008 Issue Published: 1 October 1931 PDF downloadLoading ...
Die Ursache des Carcinoms.
Authors: Van Calcar
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 15425: Is Accurate Stroke Risk ssessment with CHADS <sub>2</sub> Necessary in Managing Patients with Atrial Fibrillation? Insights from the Stroke Prevention and Rhythm Interventions in Atrial Fibrillation (SPRINT-AF) Registry
Authors: Andrew C Ha, Narendra Singh, Jafna L Cox, Paul Dorian, Carl Fournier, G.B. J Mancini, Ashfaq Shuaib, Mahesh Kajil, Michelle Tsigoulis, Milan K Gupta
Journal: Circulation (2014)

Introduction: Guidelines have advocated use of scoring schemes such as CHADS 2 to assess stroke risk for patients with atrial fibrillation (AF). However, recent studies had demonstrated poor agreement between physician-reported and scoring-derived stroke risk. From a national registry, we assessed if rates of oral anticoagulant (OAC) use differ between patients whose stroke risks are concordantly or discordantly categorized. Methods: From December 2012 to July 2013, a cross-sectional analysis of 936 consecutive AF patients was performed, enrolled from 109 primary care and specialty practices in 10 Canadian provinces. Based on clinical judgment, physicians categorized each patient as low, moderate, or high risk for stroke. We categorized patients’ stroke risk based on their CHADS 2 score (low: 0; moderate: 1, high: ≥2). Agreement between physician-reported and CHADS 2 risk was reported by the weighted kappa. We compared rates of OAC use between patients whose stroke risk was concordantly or discordantly categorized by clinicians, relative to those derived from CHADS 2 . Results: Complete data were available in 929 (98.8%) patients for analysis. The weighted kappa between physician-reported and CHADS 2 -derived stroke risk was 0.41 (95% CI: 0.34 to 0.48). Physician-determined stroke risk was concordantly categorized to CHADS 2 scores in 544 (58.6%) patients. Among patients with CHADS 2 ≥2, rates of OAC use were similar between the concordant and discordant groups (91.7% vs. 90.4%, p=0.66). For patients with CHADS 2 =1, rates of OAC use were higher in the concordant group (84.2% vs. 66.4%, p&lt;0.01). For patients with CHADS 2 =0, rates of OAC use were lower in the concordant group (43.5% vs. 80.0%, p&lt;0.01). Conclusions: In this contemporary AF registry, the agreement between physician-reported and CHADS 2 -derived stroke risk was only modest. Despite this, the rate of OAC use in patients at high risk (CHADS 2 ≥2) was similarly high between the concordant and discordant groups. However, rates of OAC use between the 2 groups differed among patients at lower stroke risk. Our results suggest that discrepancy in stroke risk categorization is associated with guideline-discordant OAC use, particularly for patients with lower CHADS 2 scores.
Nlrp3/caspase-1-independent IL-1β production mediates diesel exhaust particles-induced pulmonary inflammation
Authors: Sharen Provoost, Kurt Tournoy, Nele Pauwels, Tom Vanden Berghe, Peter Vandenabeele, Bart Lambrecht, Guy Joos, Tania Maes
Journal: European Respiratory Journal (2011)

Inhalation of diesel exhaust particles (DEP) induces an inflammatory reaction in the lung; however, the mechanisms are largely unclear. Interleukin (IL)-1β/IL-1RI signaling is crucial in several lung inflammatory responses. Typically, caspase-1 is activated within the Nlrp3 inflammasome, that recognizes several damage associated molecular patterns, which results in cleavage of pro-IL-1β into mature IL-1β.  Here, we hypothesize that the Nlrp3/caspase-1/IL-1β pathway is critical in DEP-induced lung inflammation. Upon DEP exposure, IL-1RI KO mice showed reduced inflammation in the lung when compared to WT mice. In line, treatment with recombinant IL-1R antagonist (anakinra) and IL-1β neutralization impaired the DEP-induced lung inflammatory response. Upon DEP exposure, Nlrp3 and caspase-1 KO mice, however, showed similar IL-1β levels and comparable inflammation in the lung compared to WT mice.  In conclusion, these data demonstrate that the DEP-induced inflammation in the lung acts through the IL-1β/IL-1RI axis. In addition, DEP initiates inflammation independent of the “classical” Nlrp3/caspase-1 pathway.  Funding: Fund for Scientific Research Flanders - Belgium (FWO Vlaanderen; Research Project G.0052.06 and G.0329.11N) and Interuniversity Attraction Poles (IUAP) - Belgian Science Policy P6/35.
Development of PF-05280014, a potential biosimilar to trastuzumab.
Authors: Ira A Jacobs, Reginald Ewesuedo, Donghua Yin, Ruifeng Li, Susan Hurst, Anne M. Ryan, Chee-Keng Ng, Michael W. Leach, Gregory Finch, Charles M. Zacharchuk
Journal: Journal of Clinical Oncology (2015)

618 Background: Trastuzumab, a humanized recombinant monoclonal antibody, targets HER2 and is approved for treatment of HER2-overexpressing breast and gastric cancers. PF-05280014 is being developed as a potential biosimilar to trastuzumab. Similarity of PF-05280014 to trastuzumab sourced from the EU and US (trastuzumab-EU and -US) was assessed using structural and functional, nonclinical pharmacokinetic (PK) and tolerability, and clinical studies; the toxicity of PF-05280014 was also assessed. Methods: Structural similarity was determined by peptide mapping. Functional similarity was measured using an in vitro tumor cell growth inhibition assay. Comparative PK, tolerability, and anti-drug antibody (ADA) responses were evaluated in male CD-1 mice following a single dose; PK and toxicity of PF-05280014 alone were evaluated in CD-1 mice (both sexes) after 5 doses. In a phase I study, 105 healthy male volunteers received a single 6 mg/kg IV dose of PF-05280014, trastuzumab-EU, or trastuzumab-US. Drug concentration-time data were analysed by noncompartmental methods. PK similarity was considered demonstrated for a given test-to-reference comparison if the 90% CI was within 80.00%-125.00%. Results: Peptide mapping showed PF-05280014 was similar to trastuzumab-EU and trastuzumab-US. Dose response curves in the in vitro cell growth inhibition assay were superimposable. In vivo PK profiles were similar in mice and there were no toxicity findings for PF-05280014. In the phase I study, PK similarity was shown between PF-05280014 and trastuzumab-EU and trastuzumab-US, with 90% CI of Cmax, AUCT, and AUC0-∞ within 80.00%–125.00% for each pair-wise comparison. Adverse events were similar across groups; only 1 subject (trastuzumab-EU group) was ADA positive postdose. Conclusions: Evaluation of PF-05280014 thus far supports its development as a potential biosimilar to trastuzumab. An ongoing, phase III, randomized, double-blind clinical trial is comparing PF-05280014 + paclitaxel with trastuzumab-EU + paclitaxel for first-line treatment of patients with HER2+ metastatic breast cancer. A second phase III, randomized, double-blind trial evaluating PF-05280014 in the neoadjuvant setting for breast cancer is ongoing. Clinical trial information: NCT01603264, NCT02187744, and NCT01989676.
Abstract 12326: Revised 2010 Task Force Criteria for ARVD/C Diagnosis Promote Inclusion of Non-Desmosomal Mutation Carriers
Authors: Judith A Groeneweg, Paul A van der Zwaag, Christian van der Werf, Moniek G Cox, Jan D Jongbloed, Connie R Bezzina, Ans C Wiesfeld, Jeroen F van der Heijden, Pieter A Doevendans, Arthur A Wilde, J P van Tintelen, Dennis Dooijes, Richard N Hauer
Journal: Circulation (2011)
Adults with Prader-Willi Syndrome: Abnormalities of Sleep and Behaviour
Authors: D J Clarke, J Waters, J A Corbett
Journal: Journal of the Royal Society of Medicine (1989)

A survey of 32 adult females and 31 adult males with Prader-Willi syndrome (PWS) shows that sleep disorders (including excessive day and night time sleep) and behavioural abnormalities, (temper tantrums and deliberate picking of sores) are common. These abnormalities are not related to the degree of obesity or to each other. Speech disorders also occur. Intelligence quotients are often within the normal range.
Abstract 13523: Extracorporeal Membrane Oxygenation Stimulates Myocardial Protein Synthesis without Altering Leucine Oxidation in Immature Swine in vivo
Authors: Colleen M O'Kelly Priddy, Masaki Kajimoto, Dolena R Ledee, Bertrand Bouchard, Nancy G Isern, Aaron K Olson, Christine Des Rosiers, Michael A Portman
Journal: Circulation (2011)

Introduction: Extracorporeal Membrane Oxygenation (ECMO) serves as a mechanical circulatory support bridge to recovery in children, allowing the heart to overcome severe insults such as ischemia/re...
Phase I Trial Of Autologous CD19-Targeted CAR-Modified T Cells As Consolidation After Purine Analog-Based First-Line Therapy In Patients With Previously Untreated CLL
Authors: Jae H Park, Isabelle Rivière, Xiuyan Wang, Jolanta Stefanski, Qing He, Oriana Borquez-Ojeda, Teresa Wasielewska, Clare Taylor, Jinrong Qu, Shirley Bartido, Yvette J Bernal, Michel Sadelain, Renier J Brentjens
Journal: Blood (2013)
Withdrawing life sustaining treatment and euthanasia debate
Authors: T. Woodcock, P. Biegler, N. McIntosh, M D D Bell, A. Waite
Journal: BMJ (2001)

Editor—Street and Henderson invite debate about an accepted medical practice (withdrawing life sustaining treatment under the influence of paralysing agents) that is approved by an authoritative ethical advisory committee and yet is of questionable legality.1 It should be no surprise that a course of action that is ethically justifiable may be illegal, for the law of England on care at the end of life is both morally and intellectually misshapen.2

In their commentary Inwald and Vandyck submit that the advice of the ethical committee is not compatible with the common law of England, and that to cause respiratory muscle paralysis in a patient without providing ventilatory support is a form of euthanasia. I agree with their view, but I am not confident that their proposed solution of discontinuing the administration of the paralysing drug shortly before the abrupt discontinuation of ventilation, omitting to allow the drug to be eliminated or reversed, would be accepted by a court.

Edwards tries to reconcile the practice of ventilator withdrawal under pharmacological paralysis with the legal doctrine of double effect, but she misses or avoids the point that we cannot claim that muscle relaxants are drugs necessary to alleviate suffering and primarily used for such palliation. Their lethal pharmacological effect on unventilated patients is therefore not secondary, and the practice constitutes euthanasia. Outside of its narrow legal standing, double effect is not universally accepted as a morally relevant concept.3,4 In both these commentaries the only submitted justification for not waiting the hour or two it would take to clear the drug from the system (if it has been administered in a therapeutic dose) is to claim that the delay harms the patient who is lingering on a ventilator. Given that patients given curare ought normally to be sedated or anaesthetised during pharmacological paralysis, this alleged suffering cannot be given much weight. Moreover, Lord Goff specifically rejected the compassionate avoidance of lingering as a defence against mercy killing.2

Although we can construct a strong case for the moral acceptability of euthanasia in such circumstances, it is unlikely that a court could be persuaded that the practice is legal according to England's current law. Edwards unsubstantiated statement that atracurium does not have problematic residual effects ought to be corrected.5
Abstract 3889: Antecedent Aspirin Dose and Platelet Inhibition with Clopidogrel in Patients After Coronary Stenting and Ischemic Stroke: Analysis of 711 cases of Dual Antiplatelet Therapy
Authors: Victor L Serebruany, Alex Malinin, Deepak L Bhatt, Dan Atar, Dan Hanley
Journal: Circulation (2006)
Diabetes mellitus (DM), serum glucose, and outcome in gastroesophageal (GE) cancer
Authors: J. W. Feilchenfeldt, M. Capanu, A. Farooki, D. Sully, B. Miron, D. G. Power, M. Jhawer, D. H. Ilson, D. P. Kelsen, M. A. Shah
Journal: Journal of Clinical Oncology (2009)

e15661 Background: Diabetes mellitus (DM) and impaired glucose tolerance (IGT) are frequent comorbidities in cancer patients. Their diagnosis is predictive of early recurrence following resection of colorectal cancer and of increased treatment related toxicity in localized breast cancer. Impaired glucose tolerance is a risk factor for the development of GE cancer. As nutrition and performance status are key determinants of outcome, we hypothesized that DM would influence treatment outcome in GE cancer. Our primary objective was to analyze the role of serum glucose, DM, serum albumin and BMI on treatment outcome and toxicity amongst a cohort of uniformly treated patients with GE cancer. Methods: 211 patients with GE cancer enrolled on 3 localized (2 esophagus, 1 gastric) and 4 metastatic consecutive prospective clinical trials (3 gastric, 1 esophagus) were examined. The studies involved treatment with chemotherapy combinations of taxanes, platinum, irinotecan, 5-fluorouracil, bevacizumab and cetuximab. Diagnosis of DM was based on clinical data, random glucose or fasting-glucose levels. Study parameters were tested for their association to time to treatment failure (TTF), overall survival (OS) and toxicity using the X 2 test. Results: 132 metastatic pts were included: median age 57(range 32–76), M/F 96/36, median BMI 25.3 (16.2–40.1), 19 diabetic / 113 non-diabetic; overall survival was 10.8 months. 79 patients had localized disease: median age 61(32–80), M/F=53/26, median BMI 25.8 (range 16.1–38.5), 10 diabetic/69 non-diabetic; overall survival was 23.2 months. There was no statistically significant association of random glucose (p=0.06), DM (p=0.9), or BMI(p=0.2) with survival or with treatment related toxicity. Low serum albumin was associated with reduced survival, hazard ratio 2.12 (95% CI1.5–3.2), p&lt;0.001. Conclusions: In GE cancer patients on protocol therapy, we confirm the negative prognostic significance of serum albumin on patient survival. This is remarkable considering all patients were protocol eligible with adequate organ function and performance score. We did not observe a clinically relevant impact of IGT or DM on treatment outcome or toxicity. No significant financial relationships to disclose.
Abstract 1317: A Proprotein Convertase Subtilisin-like/Kexin Type 9 (PCSK9)-binding Antibody, That Structurally Mimics the Egf-a Domain of the LDL-receptor, Lowers LDL-cholesterol in a Transgenic Mouse Model and in Rhesus Monkeys
Authors: Jon Condra, Andrea Carfi, Stefania DiMarco, Yan Ni, Weirong Wang, Matthew Bottomley, Ray Rosa, Vivienne Mendoza, Shilpa Pandit, Xun Shen, Liwen Zhang, Joseph Santoro, Timothy Fisher, Cinzia Volpari, Dale Lewis, Holly Hammond, Dana Wood, Sharon Lobo, Douglas Wisniewski, Kimberly Michel, Lora Hamuro, Thorsten Verch, David Shen, Brian Hubbard, Ayesha Sitlani
Journal: Circulation (2009)

Proprotein convertase subtilisin-like/kexin type 9 (PCSK9) regulates LDL-C levels by binding to cell surface LDL-receptor protein (LDLR) and is an important therapeutic target for treating coronary...
Genomic grade: Feasibility in routine practice and influence on treatment decision in early breast cancer.
Authors: O. Metzger, A. Catteau, S. Michiels, M. E. Buyse, K. V. Saini, V. Fasolo, J. Canon, P. Delrée, M. Coibion, V. Jossa, J. Kains, D. Larsimont, V. Richard, D. Faverly, N. Cornez, P. Vuylsteke, B. Vanderschueren, H. P. Peyro Saint Paul, M. J. Piccart-Gebhart, C. Sotiriou
Journal: Journal of Clinical Oncology (2011)

606 Background: Genomic grade index (GGI) is a 97-gene signature which improves accuracy and prognostic value of histological grading (HG) in invasive breast carcinoma (IBC). GGI is particularly useful in segregating HG2 tumors into low or high Genomic Grade (GG1 and GG3). We aimed at prospectively evaluating the feasibility to implement GGI in routine practice with the primary objective of obtaining GGI in at least 80% of fresh tumor samples collected at surgery. Secondary objectives include GGI classification performance and impact on treatment recommendations. Methods: Eligible patients were pT1pT2 or operable pT3, N0-3 IBC. Fresh surgical samples with a H&E slide representative of the tumor specimen were sent at room temperature in the MapQuantKit for centralized analysis. Genomic profiles (Affymetrix U133 Plus 2.0) were determined for samples containing ≥ 30% invasive tumor cells and GGI calculated using the Ipsogen MapQuantDx protocol, which defines tumors as GG1 or GG3. Results: Between Jan and Dec 2010, 173 pts were recruited in eight centers in Belgium and 151 were eligible (21 pts N >3, 1 pt no IBC). MapQuant test was performed in 138 cases (excluding 8 tumors too small for sampling, 3 samples forgotten, 2 with no H&E slide) and GGI was obtained in 78% of cases (n=108). Reasons for failures were: 15 samples with <30% of invasive tumor cells (11%), 14 insufficient RNA quality (10%) and 1 failed hybridization (<1%). For tumors with an available representative sample (≥ 30% inv. tumor cells) (n=123) the success rate was 88%. Of 138 tumor samples collected, 77% were N0, 81% were ER+, 10% HER2+ and 9% triple negative; median tumor size was 17mm (range 6-55). The HG1, HG2 and HG3 frequencies were 24%, 48% and 28% resp. Concordance between HG1/HG3 Histologic and GG1/GG3 Genomic grading was 90%. GGI reclassified 67% of the 52 HG2 tumors as GG1 (51%) or GG3 (49%) leading to a total of 34% GG1 (n=37), 44% GG3 (n=47) and 22% undetermined (UD) (n=24). Conclusions: Genomic Grade is feasible in routine clinical practice with a success rate of 88% when a representative tumor sample is provided. The impact of GGI on treatment decision will be presented at the meeting.