tbuckley/cabot-search huggingface dataset:
Abstract MP021: Glycated Hemoglobin and Risk of Incident Hypertension in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Julie K Bower, Lawrence J Appel, Kunihiro Matsushita, J. H Young, Alvaro Alonso, Frederick L Brancati, Elizabeth Selvin
Journal: Circulation (2012)

Introduction: Diabetes and hypertension often co-occur and have shared risk factors. While hypertension is known to predict diabetes, hyperglycemia may also be independently associated with incident hypertension. We investigated glycated hemoglobin (HbA1c) as a predictor of incident hypertension in individuals in the Atherosclerosis Risk in Communities (ARIC) cohort. Methods: We conducted a prospective analysis of 9,603 middle-aged participants in the ARIC Study without hypertension at baseline. Using Cox proportional hazards models, we estimated the association between HbA1c at baseline and incident hypertension by two definitions: (1) self-reported hypertension during a maximum of 18 years of follow-up; and (2) measured blood pressure or hypertension medication use recorded at clinic visits for a maximum of 9 years of follow-up. Results: We observed 4,800 self-reported hypertension cases and 1,670 visit-based cases. Higher baseline HbA1c was associated with increased risk of hypertension and was robust to adjustment for a comprehensive list of confounders that included two measures of adiposity (body mass index and waist-hip ratio). Compared to nondiabetic adults with HbA1c &lt;5.7%, HbA1c in the pre-diabetic range (5.7–6.4%) was independently associated with incident self-reported hypertension (HR 1.25, 95% CI: 1.16–1.34) and visit-detected hypertension (HR 1.18, 95% CI: 1.04–1.34). The HR per 1-% point higher HbA1c was 1.11 (1.06–1.16) among those with no history of diabetes and 1.06 (1.01–1.11) among those with diagnosed diabetes; the continuous associations between HbA1c and incidence of self-reported hypertension for individuals without diabetes are illustrated in the Figure. Conclusions: The association of HbA1c with incident hypertension suggests that elevated levels of circulating glucose may independently contribute to cardiovascular risk through higher blood pressure. Persons with elevated HbA1c, even without a prior diabetes diagnosis, are at increased risk of developing hypertension.
Abstract 4659: Risk of Failure of Transvenous Implantable Cardioverter Defibrillator Leads
Authors: C Jan Willem Borleffs, Lieselot van Erven, Rutger J van Bommel, Enno T van der Velde, Ernst E van der Wall, Jeroen J Bax, Frits R Rosendaal, Martin J Schalij
Journal: Circulation (2008)

Despite the positive effect on mortality in selected patients, implantable cardioverter defibrillator (ICD) therapy is also associated with potential malfunction of the implanted system. Objective ...
Prolonged G2 arrest and Chk1 overactivation following DNA damage in the absence of DNA-PK activity
Authors: Christopher M. Sturgeon, Zachary A. Knight, Kevan M. Shokat, Michel Roberge
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4435 

Cells can respond to DNA damage by activating DNA repair mechanisms and cell cycle checkpoints. In the absence of p53, the G2/M DNA damage checkpoint represents the final chance for a cell to prevent transmission of damaged DNA to daughter cells. DNA-PK is a crucial component of the non-homologous end joining (NHEJ) DNA double-strand break repair machinery. Although it belongs to the same PI3-like kinase family as ATM and ATR, it is generally believed not to have a G2 checkpoint function because it is not required to initiate G2 arrest after DNA damage. However, we show that human glioma M059J and rodent CHO V3 cells lacking the DNA-PK catalytic subunit enter a prolonged G2 arrest after exposure to ionizing radiation while their DNA-PK-proficient counterparts M059K, M059J/Fus1 and CHO V3 cells transfected with hDNA-PKcs only undergo a transient arrest. G2 accumulation is observed at the clinical-dose of 2 Gy in DNA-PK-deficient cells, while DNA-PK-proficient cells failed to exhibit any arrest at this dose. The prolonged arrest is observed up to 48 hours post-irradiation (IR) in both DNA-PK-deficient cell lines. This arrest is accompanied by a strong overactivation of Chk1, and decreased CDK1 activation. Also, the ATM/ATR inhibitor caffeine, as well as the Chk1/Chk2 inhibitor isogranulatimide (Jiang et al., 2004. Mol. Can. Ther. 3:1221) exhibit decreased activity in DNA-PKcs deficient cells, indicating a strengthened checkpoint response. Prolonged G2 arrest is similarly observed when DNA-PK-proficient cells are exposed to the selective DNA-PK inhibitor AMA37 (Knight et al., 2004. Bioorg. Med. Chem. 12:4749), but not when cells are exposed to 200 nM wortmannin. This arrest is dependent on maintaining DNA-PK inhibition, which must be present at the time irradiation. Irradiation of M059 cells in late-S/G2 caused no prolonged arrest, suggesting the role DNA-PK plays in the maintenance of the G2 checkpoint lies in its NHEJ function, with DNA lesions leading to an extended checkpoint response.
Abstract 2455: Intensive Statin Therapy Reduces Risk of Cardiovascular Disease Beyond Occurrence of the First Event: Analysis of the Incremental Decrease in Endpoints through Aggressive Lipid Lowering Trial
Authors: Matti Tikkanen, Michael Szarek, Nilo B Cater, Ingar Holme, Ole Faergeman, John J Kastelein, Anders G Olsson, Christina Lindahl, Terje R Pedersen
Journal: Circulation (2007)
Pemetrexed plus cetuximab in patients (pts) with recurrent non-small cell lung cancer (NSCLC): A phase I-IIa dose-ranging study from the Hoosier Oncology Group
Authors: S. I. Jalal, D. Waterhouse, M. Edelman, S. Nattam, R. Ansari, K. Koneru, M. Yu, J. Shen, T. Breen, N. Hanna
Journal: Journal of Clinical Oncology (2007)

7698 Background: Both pemetrexed (P) and cetuximab (C) have single agent activity in NSCLC, non-overlapping toxicities and different mechanisms of action, making the combination of P and C an attractive option to evaluate. This study evaluates the feasibility of combining these agents, and tests the activity and toxicity of this regimen in pts with recurrent NSCLC. Methods: Eligible pts had stage IIIB/IV NSCLC, previously treated ≥ 1 prior platinum containing regimen, PS 0–1. Prior use of EGFR tyrosine kinase inhibitors was permitted. The phase I portion determined the MTD (Bedano Proc ASCO et al., 2006). The primary endpoint of the phase II portion was to estimate TTP using Kaplan-Meier analysis (5% alpha, 80% beta), requiring 25 pts to demonstrate a TTP of ≥ 24 weeks vs. historical control of 12 weeks. Following a loading dose of C at 400 mg/m 2 on week 1, pts received P at 750 mg/m 2 iv q3wks and C at 250 mg/m 2 iv weekly. Cycles were repeated every 21 days. After completing at least 4 cycles, pts with non-progressive disease (PD) were allowed to continue C alone until PD. Results: Eligible and treated phase II pts (n=23) received a median of 4 cycles (range 1–12). Pt characteristics: M:F 57%:43%; median age 64 (range 43–80), stage IIIB: IV 17%:83%; adeno:squamous cell 61%:30%; smoking status: current/former/never: 29%/62%/10%. Prior regimens, median 2 (range 1–6). G3/4/5 toxicities included: 4.3% neutropenia, 13% infection, 4.3% hemorrhage, 22% skin. There were no G3/4 episodes of anemia, TCP, febrile neutropenia, liver toxicity or diarrhea. Response data was available for 18 patients. Partial responses were seen in 2 pts (8.7 %), SD in 8 patients (34.8%). Median TTP was 25 weeks. Conclusion: It is feasible and safe to combine P at 750 mg/m 2 every 21 days and C at 400 mg/m 2 week 1 and 250 mg/m 2 weekly thereafter. This combination resulted in longer TTP when compared with historical controls of P at 500 mg/m 2 alone. No significant financial relationships to disclose.
Abstract 10777: Metformin Impairs Vascular Endothelial Recovery After Stent Placement In the Setting of Locally Eluted mTOR inhibitors via S6K Dependent Inhibition of Cell Proliferation
Authors: Anwer Habib, Vinit Karmali, Rohini Polavarapu, Masataka Nakano, Saami Yazdani, Fumiyuki Otsuka, Kim Pachura, Talina Davis, Jagat Narula, Frank D Kolodgie, Renu Virmani, Aloke V Finn
Journal: Circulation (2012)

Introduction: Treatment of diabetic patients with coronary artery disease involve medical therapy and coronary intervention with drug eluting stents (DES) most of which elute mechanistic target of ...
Favorable Results of Allo-HSCT from MRD in Patients with Myelofibrosis
Authors: Miroslaw Markiewicz, Monika Dzierzak-Mietla, Patrycja Zielinska, Agata Wieczorkiewicz-Kabut, Sylwia Mizia, Mariusz Matyja, Krzysztof Bialas, Grzegorz Helbig, Anna Koclega, Malwina Rybicka, Lech Sedlak, Tomasz Oleksy, Slawomira Kyrcz-Krzemien
Journal: Blood (2014)
SENSITIVITY TO PEANUT OIL WITH THE REPORT OF A CASE
Authors: Francis H. Chafee
Journal: Annals of Internal Medicine (1941)

Case Reports1 December 1941SENSITIVITY TO PEANUT OIL WITH THE REPORT OF A CASEFRANCIS H. CHAFEE, M.D., F.A.C.P.FRANCIS H. CHAFEE, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-15-6-1116 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSince Keeney1 in 1938 first reported the use of a slowly absorbed epinephrine preparation, allergists have found that the use of epinephrine in oil is of great value in controlling intractable asthma. Epinephrine in peanut oil is now available commercially. Although there are few reports in the literature definitely indicating that peanut oil may act as an atopen, there are records of unusual reactions to this preparation.In 1939 Keeney2reported one instance in which urticaria developed after daily use of epinephrine in peanut oil for six weeks. This occurred along with a flare-up of an old sinusitis, and whether...References1. KEENEY EL: Slowly absorbed epinephrine preparation, preliminary report, Bull. Johns Hopkins Hosp., 1938, lxii, 227. Google Scholar2. KEENEYPIERCEGAY ELJALN: Epinephrine in oil; a new slowly absorbed epinephrine preparation, Arch. Int. Med., 1939, lxiii, 119. CrossrefGoogle Scholar3. MURPHYJONES JACA: Slow epinephrine in the treatment of chronic asthma, Jr. Allergy, 1939, x, 215. CrossrefGoogle Scholar4. COHN J: Unusual reactions to slow epinephrine, Jr. Allergy, 1939, x, 459. CrossrefGoogle Scholar5. LEVISONHARRISON LAJJ: Dermatitis following Theelin, Jr. Am. Med. Assoc., 1939, cxiii, 2055. Google Scholar6. DAVIS ES: Correspondence, Jr. Am. Med. Assoc., 1940, cxiv, 1285. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Providence, Rhode Island*Received for publication June 10, 1940. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byFood allergy to sunflower oil in a patient sensitized to mugwort pollenFood allergy to sunflower oil in a patient sensitized to mugwort pollenRisks of milk formulas containing peanut oil contaminated with peanut allergens in infants with atopic dermatitisContact urticaria from peanut butter 1 December 1941Volume 15, Issue 6Page: 1116-1117KeywordsAsthmaEpinephrineOilsUrticaria Issue Published: 1 December 1941 PDF downloadLoading ...
Abstract 9164: Who Receives ASA for Primary Prevention in Canada?: Insight From the PRIMARY CARE AUDIT OF GLOBAL RISK MANAGEMENT (PARADIGM) Study
Authors: Milan Gupta, Ilia Ostrovski, Mahesh Kajil, Michelle Tsigoulis, Subodh Verma
Journal: Circulation (2011)

BACKGROUND: The role of ASA for primary CVD prevention is controversial. We assessed the use of ASA in healthy, middle-aged subjects in the PARADIGM study. METHODS: PARADIGM enrolled 3015 men &gt;40 or women &gt;50 to assess trends in CV risk assessment. Subjects with diabetes, vascular disease, or those receiving lipid lowering drugs were excluded. We report on the 406 subjects (13.5%) who were receiving ASA for primary CVD prevention. RESULTS: Subjects prescribed ASA, compared to those not, were more likely to be older (61.6 vs. 55.5y, p&lt;0.0001), male (p&lt;0.001), white Caucasian (88.9 vs. 66.6%, p&lt;0.0001), past/current smokers (43.8 vs. 33.3%, p=0.0004), hypertensive (60.8 vs. 25.7%, p&lt;0.00001), and to have a CV family history (30.9 vs. 23.3%, p=0.002). SBP, DBP, creatinine, hsCRP, waist circumference (WC) and BMI were discriminators of ASA use (all p&lt;0.0005). LDL-c fasting glucose, IFG, and HbA1c did not differ between those prescribed ASA or not. Mean modified FRS for those prescribed ASA vs. not were 22.3 vs. 13.5% respectively (p&lt;0.00001). Of those prescribed ASA, FRS categories were 18% low, 47.8% intermediate, and 34.2% high. In ASA-treated subjects, rates of smoking, HT, family history and mean BP, BMI and hsCRP were similar between genders. Mean HDL and LDL (both p&lt;0.0001), glucose (p=0.05), and HbA1c (p=0.0001), were higher in women than men. Mean FRS was lower in ASA-treated women (14.4 vs. 27.0%, p&lt;0.00001). FRS categories for ASA-treated women vs men were: low (34.4 vs 8.2%), intermediate (43 vs. 34.5%), and high (22.5 vs. 57.3%, all p&lt;0.00001). CONCLUSIONS: In PARADIGM, 13.5% of men &gt;40 and women &gt;50 received ASA for primary CVD prevention. Smoking, HT, family history, hsCRP and abdominal obesity were discriminators of ASA use, yet lipid and glycemic levels were not. Two thirds of ASA-treated subjects had low/intermediate FRS. The majority of ASA use in women was in those with low or intermediate risk scores.
Accurate Characterization of Skeletal Lesions in Tuberous Sclerosis Complex Using 99mTc MDP SPECT/CT
Authors: Girish Kumar Parida, Varun Singh Dhull, Sellam Karunanithi, Saurabh Arora, Anshul Sharma, Shamim Ahmed Shamim
Journal: Clinical Nuclear Medicine (2015)

We report a 15-year-old patient with tuberous sclerosis complex or Bourneville's disease with history of generalized tonic-clonic seizure for last 2 years and was currently on antiepileptic medication. He also had a history of left nephrectomy for renal cell carcinoma clear cell type. The patient had multiple adenoma sebaceum over the nasolabial region, ash leaf spots over the lower limbs, a Shagreen patch over the back, and multiple calcified tubers in the subependymal region. He was then referred for the skeletal scintigraphy to look for skeletal lesions, which revealed involvement of bilateral humeri, tibiae, and iliac bones accurately characterized on SPECT/CT.
Post-Transplantation Cyclophosphamide and Mesenchymal Stem Cells Infusion For Graft-Versus-Host Prophylaxis For Patients With Advanced Disease After Allogenic Bone Marrow Transplantation
Authors: Mikhail Drokov, Elena Parovichnikova, Larisa Kuzmina, Vera Vasilyeva, Alexandra Karyakina, Gennadyi Galstian, Valeri G. Savchenko
Journal: Blood (2013)
Full-Body MRI in Patients With an Implantable Cardioverter-Defibrillator
Authors: Michael R. Gold, Torsten Sommer, Juerg Schwitter, Ahmed Al Fagih, Timothy Albert, Béla Merkely, Michael Peterson, Allen Ciuffo, Sung Lee, Lynn Landborg, Jeffrey Cerkvenik, Emanuel Kanal
Journal: Journal of the American College of Cardiology (2015)

Magnetic resonance imaging (MRI) of patients with conventional implantable cardioverter-defibrillators (ICD) is contraindicated.This multicenter, randomized trial evaluated safety and efficacy of a novel ICD system specially designed for full-body MRI without restrictions on heart rate or pacing dependency. The primary safety objective was >90% freedom from MRI-related events composite endpoint within 30 days post-MRI. The primary efficacy endpoints were ventricular pacing capture threshold and ventricular sensing amplitude.Subjects received either a single- or dual-chamber ICD. In a 2:1 randomization, subjects either underwent MRI at 1.5-T of the chest, cervical, and head regions to maximize radiofrequency exposure up to 2 W/kg specific absorption rate and gradient field exposure to 200 T/m/s per axis (MRI group, n = 175), or they underwent a 1-h waiting period without MRI (control group, n = 88). A subset of MRI patients underwent ventricular fibrillation induction testing post-MRI to characterize defibrillation function.In 42 centers, 275 patients were enrolled (76% male, age 60.4 ± 13.8 years). The safety endpoint was met with 100% freedom from the composite endpoint (p < 0.0001). Both efficacy endpoints were met with minimal differences in the proportion of MRI and control patients who demonstrated a ≤0.5 V increase in ventricular pacing capture threshold (100% MRI vs. 98.8% control, noninferiority p < 0.0001) or a ≤50% decrease in R-wave amplitude (99.3% MRI vs. 98.8% control, noninferiority p = 0.0001). A total of 34 ventricular tachyarrhythmia/ventricular fibrillation episodes (20 induced; 14 spontaneous) occurred in 24 subjects post-MRI, with no observed effect on sensing, detection, or treatment.This is the first randomized clinical study of an ICD system designed for full-body MRI at 1.5-T. These data support that the system is safe and the MRI scan does not adversely affect electrical performance or efficacy. (Confirmatory Clinical Trial of the Evera MRI System for Conditionally-Safe MRI Access; NCT02117414).
Fortnightly Review: Commentary: The perils of checklist medicine
Authors: I. Heath
Journal: BMJ (1995)

This paper has a logic and clarity that does not seem to belong in the messy world where I and my patients strive, often against daunting socioeconomic odds, to be “co-producers of health.”1 The honourable intentions of the authors are evident, but the notion of defining and using criteria with which purchasers can monitor compliance with agreed guidelines implies levels of coercion and control which are potentially destructive of the fragile good that is the doctorpatient relationship.2 Guidelines are constructed from evidence from research derived from studies of populations and are predicated on the notion of a composite patient which may have little immediate relevance to the troubled person who presents in …
Atrial Fibrillation Activates AMP-Dependent Protein Kinase and its Regulation of Cellular Calcium Handling
Authors: Masahide Harada, Artavazd Tadevosyan, Xiaoyan Qi, Jiening Xiao, Tao Liu, Niels Voigt, Matthias Karck, Markus Kamler, Itsuo Kodama, Toyoaki Murohara, Dobromir Dobrev, Stanley Nattel
Journal: Journal of the American College of Cardiology (2015)
Abstract 229: The Novel Angiogenic Cytokine Secretoneurin promotes Angiogenesis, Arteriogenesis and Vasculogenesis in the Hind-Limb Ischemia Model
Authors: Wilfried Schgoer, Margot Egger, Arno Peer, Johannes Jeschke, Ivan Tancevski, Andreas Ritsch, Hildegunde Piza-Katzer, Josef R Patsch, Peter Schratzberger, Rudolf Kirchmair
Journal: Circulation (2007)

Introduction - Secretoneurin (SN) represents a sensory, inflammatory neuropeptide which was recently demonstrated to act as an angiogenic and vasculogenic cytokine in vitro and in vivo. The present study was conducted to test the hypothesis that SN may be implicated in reparative angiogenesis. Furthermore, we challenged the healing potential of SN applied as a newly generated SN gene therapy vector in the setting of limb ischemia. Methods and Results - We cloned the human SN coding sequence into the pAAV plasmid containing a cytomegalovirus enhancer/promoter sequence. Bioactivity of recombinant SN was shown by proliferative and chemotactic activity on endothelial cells in vitro. Unilateral limb ischemia was induced in C57/bl mice by femoral artery resection. By Real Time PCR, Western Blotting, SN-specific RIA and Immunhistochemistry, we documented that SN is up-regulated in ischemic muscles. Next, we tested whether SN gene therapy may exert curative effects in this ischemia model. Injection of the SN plasmid into ischemic adductor muscles increased capillary (0.67 vs. 0.35, n = 24, p = 0.02) and arteriole (0.16 vs. 0.8, n = 24, p = 0.04) density, reduced endothelial cell apoptosis, and accelerated perfusion recovery as shown by Laser Doppler Perfusion Index (LDPI ratio ischemic/control leg after 28 days of ischemia 1.1 vs. 0.7, n = 24, p &lt; 0.01) in comparson to pAAV-GFP (green-fluorescence protein) treated mice. Furthermore, SN gene therapy significantly reduced toe necrosis of ischemic limbs compared to control animals (26% vs. 50%, n = 24, p &lt; 0.05). In bone marrow transplantation models, increased vascularity of ischemic hind-limbs after SN gene therapy was shown to be mediated, at least in part, by enhanced recruitment of bone marrow-derived endothelial progenitor cells. Conclusions -These results suggest that the novel angiogenic cytokine Secretoneurin is up-regulated by ischemia in skeletal muscle cells. Furthermore, results from gene therapy in this ischemia model suggest that Secretoneurin represent a promising new substance for therapeutic angiogenesis.
Abstract 5093: Genetically Elevated Lipoprotein(a) and Risk of Myocardial Infarction - a Positive Mendelian Randomization Study
Authors: Pia Kamstrup, Anne Tybjærg-Hansen, Rolf Steffensen, Børge G Nordestgaard
Journal: Circulation (2008)

Background: High levels of lipoprotein(a) (Lp(a)) associate with increased risk of myocardial infarction (MI). We tested whether this is a causal effect using a Mendelian randomization design. Methods: We genotyped for the Lp(a) kringle IV type 2 (KIV-2) size polymorphism, which explains 21% of variation in plasma levels of Lp(a). We used a cohort study of the Danish general population, The Copenhagen City Heart Study, including 9867 individuals followed for up to 16 years during which time 599 developed MI, and a case-control study, The Copenhagen Ischemic Heart Disease Study, including 1118 MI patients and 2234 controls. Results: First, increased plasma levels of Lp(a) associated with increased risk of MI (Lp(a) tertiles, trend: p&lt;0.001). Second, number of KIV-2 repeats inversely associated with Lp(a) levels: mean Lp(a) levels were 56, 31, 20, and 15 mg/dL for the 1 st , 2 nd , 3 rd , and 4 th quartile of KIV-2 repeats, respectively (trend, p&lt;0.001, Figure ). Third, multifactorially adjusted hazard ratios for MI were 1.6(95% CI:1.3–.2.0), 1.3(1.0 –1.7), and 1.1(0.9 –1.4) for individuals in the 1 st , 2 nd , and 3 rd quartile, respectively, as compared to individuals in the 4 th quartile of KIV-2 repeats (Figure ). Finally, in the case-control study, multifactorially adjusted odds ratios for MI were 1.5(1.2–1.9), 1.3(1.0 –1.6), and 1.2(1.0 –1.5) for individuals in the 1 st , 2 nd , and 3 rd quartile, respectively, as compared to individuals in the 4 th quartile of KIV-2 repeats. Conclusion: Since Lp(a) levels predict MI, and since Lp(a) KIV-2 genotype predicts both life-long increased Lp(a) levels and MI, increased Lp(a) levels appear to directly cause MI. Figure. Levels of lipoprotein (a) and risk of myocardial infarction by KIV-2
Abstract 16453: Comparable Effects of Beta-blockers on Atrial Fibrillation Promotion and Atrial Remodeling in Dogs with Atrial Tachycardia. Beyond the Beta-blocking Action
Authors: Hiroyuki Motoda, Akiko Shiroshita-Takeshita, Tomoko Morikawa, Kazuhiko Sekine, Shinya Abe, Masaru Suzuki, Shingo Hori, Satoshi Ogawa, Keiichi Fukuda
Journal: Circulation (2010)

Background: Beta-blockers are widely used for rate control in atrial fibrillation (AF). On the other hand, there is evidence that oxidative stress and inflammation contribute to the pathophysiology...