tbuckley/cabot-search huggingface dataset:
Abstract 3091: The Clinical and Electrocardiographic Phenotype of Unrelated Patients with Genotype-Negative Long QT Syndrome
Authors: Malek M El Yaman, David J Tester, Argelia Medeiros Domingo, Carla M Haglund, Michael J Ackerman
Journal: Circulation (2008)

Long QT syndrome (LQTS) is a heterogeneous group of channelopathies characterized by increased risk of potentially lethal ventricular arrhythmias. LQT1, LQT2, and LQT3 comprise 95% of genetically proven cases and exhibit a number of established genotype-phenotype correlations. The study aimed at examining the phenotypes of genotype-negative LQTS, accounting for ~25% of LQTS cases. An IRB-approved retrospective analysis was conducted on 56 patients (39 female, 25 ± 17 years) who, after genetic testing either in our sudden death genomics laboratory or with the commercially available Familion test, were negative for mutations in the 3 principal LQTS-susceptibility genes ( KCNQ1, KCNH2, and SCN5A), and the minor genes underlying LQT5 and LQT6. All had been diagnosed with LQTS, with a clinical diagnostic score of ≥ 3.5 or QTc ≥ 480 ms. The mean diagnostic score was 4.4 (95% CI 4.2 – 4.7); mean QTc was 525 ms (95% CI 508 – 543 ms). Two-thirds were symptomatic (syncope, cardiac arrest, and/or seizures) with exercise-triggered events in 10 (26%). Twenty-one (38%) had a family history of sudden cardiac arrest. ECG showed a T wave pattern suggestive of LQT1 in 32%, LQT2 in 43%, and LQT3 in 18%. In those with exercise-induced symptoms, the ECG was LQT2-like in 50% and LQT1-like in 30%. One patient had post-partum syncope with an LQT2-like ECG. None had an auditory trigger, but 3 patients, all with an LQT2-like ECG, had a family history of auditory-triggered events. One-third of the patients had received an ICD, 58% as secondary prevention. Over 2/3 were on beta-blockers. Among the 45 patients so far tested for mutations in minor LQTS-susceptibility genes, 2 had LQTS-causing mutations in ANKB (LQT4), 1 in SCN4B (LQT10), 1 in AKAP9 (LQT11) and 2 in SNTA1 (LQT12). Genotype-negative patients with a firm LQTS diagnosis show marked phenotypic heterogeneity, suggesting multiple underlying pathogenic pathways. Only a few patients have LQTS-causing mutations in minor genes after complete LQT1–12 genetic testing. Classifying genotype negative patients into LQT1-, LQT2-, or LQT3-like profiles may guide the discovery of novel genes encoding channel interacting proteins corresponding to those specific signaling pathways.
Abstract 13220: Plaque Composition Analyzed by iMap-Intravascular Ultrasound Predicts Thin-Cap Fibroatheroma Determined by Optical Coherence Tomography
Authors: Seiji Koga, Satoshi Ikeda, Tomoo Nakata, Takeo Yoshida, Masayoshi Takeno, Yuji Koide, Koji Maemura
Journal: Circulation (2012)

Background: Intracoronary imaging using novel iMap-intravascular ultrasound (iMap-IVUS) can generate objective and quantitative information about coronary plaque characteristics. The present study ...
Abstract 9710: Hydrogen Sulfide Increases Nitric Oxide Production by Calcium-Dependent Activation of Endothelial Nitric Oxide Synthase
Authors: Michiya Kida, Toru Sugiyama, Takanobu Yoshimoto, Yukio Hirata
Journal: Circulation (2011)

Purpose: Hydrogen sulfide (H 2 S), which has been regarded as a toxic gas, was recently discovered to be synthesized in mammalian tissues by several different enzymes, such as cystathionine gamma-lyase (CSE), cystathionine beta-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST). Many studies have shown that H 2 S has various physiological functions, including vasodilator and antihypertensive effects in cardiovascular system. Therefore, H 2 S is considered as one of endothelium-derived relaxing factors (EDRFs). However, intracellular mechanisms of H 2 S-induced vasodilation and its interactions between other EDRFs, such as nitric oxide (NO), still remain unclear. In the present study, we investigated whether H 2 S directly regulates endothelial NO synthase (eNOS) activity and NO production in endothelial cells. Methods: We treated bovine aortic endothelial cells (BAEC) with a hydrogen sulfide donor (NaHS) and determined NO production from BAEC into the culture medium by fluorometric measurement with 2,3-diaminonaphthalene. We determined the changes of intracellular calcium concentration by using Fura 2-AM, and analyzed the activity of eNOS by western blotting. Results: NaHS dose-dependently (12.5 - 200 µM) increased NO production from BAEC with 2.6-fold increase (n=8, p&lt;0.01) by 200 µM. This NaHS-induced NO production was abolished by an intracellular calcium-chelator (BAPTA-AM), but was not affected by the inhibitor of phosphatidylinositol 3-kinase (wortmannin). This effect was partially blocked by a ryanodine receptor inhibitor (dantrolene) and an inositol 1,4,5-trisphosphate receptor inhibitor (xestosponginC). NaHS induced relatively slow increases in the intracellular calcium by 11.3 ± 1.1 nM after 15 minutes (n=4, p&lt;0.01). NaHS induced phosphorylation of eNOS at the activating phosphoserine residue 1179. This effect was completely blocked by BAPTA-AM, but wasn't affected by wortmannin. Conclusions: H 2 S directly acts on endothelial cells to induce eNOS activation and NO production by releasing calcium from the intracellular store in endoplasmic reticulum, which may explain one of mechanisms of its vasodilator function as an EDRF.
Soundings: Church parade
Authors: Colin Douglas
Journal: BMJ (1999)

I quite enjoy church parades—in moderation of course. In agnostic middle age there are complex pleasures in revisiting our national religion perhaps once or twice a year, singing its hymns, listening to the kind of scholarly, liberal sermon still sometimes heard in Scotland, and doing so in the company of agreeable and like minded colleagues.

We gather early, to stroll and gossip in the great hall where the procession is marshalled for the short walk across a cobbled square and into the cathedral. Everyone who should be here is here: variously robed, gowned, capped, and preened, representatives of the colleges, ancient and learned societies, the universities, the professions, and the armed forces—successful contented bourgeois Scotland, dressed to pray.

“Are you the physicians?” a politely agitated middle aged lady inquires. We are. “I’m sorry to bother you, but it looks as though someone’s collapsed.... Quite poorly.... So I wondered....” The two of us nearest to her, actually a physician and a surgeon, head off up the hall.

At first glance the collapse victim is worse than just poorly: pulseless, but pupils not quite dilated. My surgical colleague, by happy chance also my instructor a few years ago on a trauma life support course, does the decent surgical thing and opts for the mouth to mouth role.

Like riding a bike, thumping a chest is a skill of your youth it is hard to forget. The urgency, the rhythm, the resistance—unlike that of any model—and the underlying purpose are all once more instantly familiar and in this case effective. My colleague bravely breathes. I thump. Our patient’s pupils stay down. Time passes.

Other colleagues kindly relieve us. Eventually ambulance people arrive. An electrocardiograph shows ventricular fibrillation. Defibrillation helps. Soon a mobile intensive care team shows up too. Apart from the victim and his various helpers, the hall is now empty. In due course a second, less tidy procession, including a stretcher, straggles down the great stairway.

In church my surgical colleague reads the first lesson as though butter would not melt in her mouth. On Monday afternoon when I ring the coronary care unit the news is good: the recently condemned man is pink, cheerful, talkative, though still a little forgetful, and has just finished a three course lunch.
Abstract 3281: Oklahoma Nitrone-007: A novel compound for treating pediatric glioblastoma
Authors: Samantha Mallory, Rene McNall-Knapp, Patricia Coutinho deSouza, Kar-Ming Fung, Debra Saunders, Nataliya Smith, Shanna Smartwood, Rheal Towner
Journal: Cancer Research (2015)

Abstract Brain tumors are the most common solid tumor in children, and despite current treatment options including surgical resection, chemotherapy, and radiation for pediatric high-grade gliomas, survival in these patients remains very poor. This research represents promising pre-clinical data of a novel compound, OKN-007 (OKlahoma Nitrone 007, a disulfonyl derivative of α-phenyl-tert-butyl nitrone (PBN)), as a new clinical therapy for pediatric high-grade gliomas (pHGGs). The objective is to establish if pHGGs, which are often hard to surgically resect, can be treated with OKN-007, either as a single agent or in combination with currently used chemotherapeutic agents. OKN-007 may be an ideal candidate that can have an anti-cancer effect on pHGG cells, due to its multiple anti-cancer effects, including induction of apoptosis, and inhibition of cell proliferation and angiogenesis, and may play an important role in the anti-cancer activity against pHGGs. Morphological magnetic resonance imaging (MRI) of xenograft nude athymic and SCID mice injected with pHGG cells TCCC3752 and KNS42 is used in this study to assess brain tumor volumes for response to therapy. Preliminary data regarding the regression of pHGGs in mice following treatment with OKN-007 is presented. Mean animal survival was found to be significantly increased with OKN-007 treatment in responsive animals compared to an untreated group, p&amp;lt;0.05. Immunohistochemistry and microarray will be used to assess levels of angiogenic (VEGF (vascular endothelial growth factor), HIF-1α (hypoxia inducible factor-1α), MVD (microvessel density)), cell differentiation (CAIX (carbonic anhydrase IX)), cell proliferation (Glut-1 (glucose transporter 1), MIB-1), apoptosis (cleaved caspase 3) markers and assess inhibition of TGFB and PDGFR complexes and downstream pathways, which are overexpressed in tumors and thought to play a role in oncogenesis and progression. OKN-007 is currently an investigational drug undergoing clinical trial evaluation for recurrent gliomas in adult patients but will still require FDA approval for use in pediatric glioma patients. An outcome of the proposed research is to incorporate the pre-clinical data in an IND application to the FDA in order to translate this research to the clinic and benefit children with pHGGs. Citation Format: Samantha Mallory, Rene McNall-Knapp, Patricia Coutinho deSouza, Kar-Ming Fung, Debra Saunders, Nataliya Smith, Shanna Smartwood, Rheal Towner. Oklahoma Nitrone-007: A novel compound for treating pediatric glioblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3281. doi:10.1158/1538-7445.AM2015-3281
Abstract 18041: The Impact of Bystander CPR on Defibrillation-Survival curve in Out-of-hospital Cardiac Arrest From All-Japan Utstein Registry Data
Authors: Naohiro Yonemoto, Hiroyuki Yokoyama, Ken Nagao, Takeshi Kimura, Hiroshi Nonogi
Journal: Circulation (2011)

[Background] The study objective was the effect of time to chain of survival from out-of-hospital cardiac arrest. Several studies had the effects of them on survival from sudden cardiac arrest. These studies were estimated from medium sample size before guideline 2005. [Method] We used All-Japan Utstein Registry of the Fire and Disaster Management Agency with a prospective, population based, involving consecutive patients with an out-of cardiac arrest with witness with layperson, over 18 years, from April 1, 2006 to December 31 2009. The primary outcome measure was survival and good neurological outcome; CPC 1 or 2. We evaluated the effect and described the relationship of intervals from collapse to defibrillator with or without bystander CPR for the outcome. [Results] 19993 adults were included in the analysis. The medium time to bystander CPR was 2 minutes. The medium time to defibrillation was 12 minutes (Figure). Adjusted odds ratio of the average effect of interval from collapse to bystander CPR per a minute was 1.09 and 95% Confidence Intervals (CI) 1.07 to 1.11. Adjusted odds ratio of the average effect of interval from collapse to defibrillator with bystander CPR per a minute was 1.11 and 95%CI 1.10 to 1.12. Adjusted odds ratio of the average effect of interval from collapse to defibrillator without bystander CPR per a minute was 1.12 and 95%CI 1.11 to 1.14. The effect of time to defibrillator with bystander CPR was better outcome than the effect of time to defibrillator without bystander CPR. [Conclusions] Proportion of survival with good neurological outcome cardiac arrest differently decreased with time that defibrillation with or without bystander CPR was delayed. Bystander CPR before defibrillation showed better neurological outcome and gained about 5 minutes to obtain the same proportion of the survival without bystander CPR. Our results suggest the effect of times to the chain of survival from nationwide large population data.
The impact of broadened civil commitment standards on admissions to state mental hospitals
Authors: G L Pierce, M L Durham, W H Fisher
Journal: American Journal of Psychiatry (1985)

In 1979, the state of Washington broadened its criteria governing the involuntary commitment of the mentally ill. This study examined the impact of the revised law on involuntary and voluntary admissions and on the type of patient admitted to state hospitals in Washington. The short-term effect of the law was an abrupt increase in involuntary commitments, with a concomitant but not offsetting decline in voluntary admissions. Although the law resulted in a substantial change in admissions policy, it does not appear to have altered the type of patient admitted to state mental hospitals in Washington.
Abstract 10585: Vitamin D and Risk of Cardiovascular and Non-Cardiovascular Mortality: A Prospective Cohort Study and Meta-Analysis
Authors: Jonathan R Emberson, Joseph Tomson, Mike Hill, Jane Armitage, Dave Leon, Astrid Fletcher, Rory Collins, Robert Clarke
Journal: Circulation (2011)

Background: Low circulating vitamin D concentrations have been linked with higher risks of cardiovascular (CVD) mortality, but whether this association is causal is uncertain. We report 13-year dat...
Effects of lithium carbonate on associative productivity and idiosyncrasy in bipolar outpatients
Authors: Eric D. Shaw, J. John Mann, Peter E. Stokes, Alan Z. Manevitz
Journal: American Journal of Psychiatry (1986)

To determine the effect of lithium carbonate on the productivity and idiosyncrasy of written associations of euthymic outpatients with affective disorder, the authors assessed 22 patients at weekly intervals during lithium treatment, 2 consecutive weeks of placebo, and 2 consecutive weeks after lithium was resumed. Lithium discontinuation produced a significant increase in associational productivity and a demonstrable increase in associative idiosyncrasy, and restoration of lithium dose significantly reversed both effects. The results suggest that lithium may affect the underlying neuropsychological functions critical to the ability to generate associations and indicate the need for further study of lithium's effects on these and other functions that may relate to neuropsychological and creative processes.
Prognostic signature and clonality pattern of recurrently mutated genes in inactive chronic lymphocytic leukemia
Authors: A M Hurtado, T-H Chen-Liang, B Przychodzen, C Hamedi, J Muñoz-Ballester, B Dienes, M D García-Malo, A I Antón, F de Arriba, R Teruel-Montoya, F J Ortuño, V Vicente, J P Maciejewski, A Jerez
Journal: Blood Cancer Journal (2015)

Abstract An increasing numbers of patients are being diagnosed with asymptomatic early-stage chronic lymphocytic leukemia (CLL), with no treatment indication at baseline. We applied a high-throughput deep-targeted analysis, especially designed for covering widely TP53 and ATM genes, in 180 patients with inactive disease at diagnosis, to test the independent prognostic value of CLL somatic recurrent mutations. We found that 40/180 patients harbored at least one acquired variant with ATM ( n =17, 9.4%), NOTCH1 ( n =14, 7.7%), TP53 ( n =14, 7.7%) and SF3B1 ( n =10, 5.5%) as most prevalent mutated genes. Harboring one ‘sub-Sanger’ TP53 mutation granted an independent 3.5-fold increase of probability of needing treatment. Those patients with a double-hit ATM lesion (mutation+11q deletion) had the shorter median time to first treatment (17 months). We found that a genomic variable: TP53 mutations, most of them under the sensitivity of conventional techniques; a cell phenotypic factor: CD38-positive expression; and a classical marker as β2-microglobulin, remained as the unique independent predictors of outcome. The high-throughput determination of TP53 status, particularly in this set of patients frequently lacking high-risk chromosomal aberrations, emerges as a key step, not only for prediction modeling, but also for exploring mutation-specific therapeutic approaches and minimal residual disease monitoring.
Abstract 2805: Assessment of Coronary Artery Disease Using Magnetic Resonance Coronary Angiography: A Multicenter Trial
Authors: Shingo Kato, Hajime Sakuma, Nanaka Ishida, Masaki Ishida, Motonori Nagata, Yasutaka Ichikawa, Kazuhiro Kataoka, Yuji Matsumoto, Hiroshi Seo, Reiji Ochiai, Koga Hosp, Yasuyuki Kobayashi
Journal: Circulation (2008)

Background: CT coronary angiography is widely used to assess the presence of significant coronary artery disease (CAD). However, CT approach is associated with low but nonnegligible cancer risk. The purpose of this prospective multicenter study was to evaluate the diagnostic performance of coronary magnetic resonance angiography (MRA) in the ability to identify patients with significant CAD compared with coronary angiography. Materials and Methods: The subjects were recruited from 7 institutions. Free breathing coronary MR angiograms covering the entire coronary artery tree were obtained in 138 patients who were suspicious of CAD. Non-contrast enhanced images were acquired with a commercial 1.5T MR imager and five-element cardiac coils after sublingual administration of isosorbide dinitrate. Conventional X-ray coronary angiography was performed within 4 weeks after coronary MRA. MR and X-ray angiograms were sent to a core laboratory for blinded interpretation. Coronary MR angiograms were evaluated by two experienced investigators by using sliding partial MIP reconstruction. Quantitative X-ray coronary angiography analysis was performed with significant CAD defined as luminal narrowing of at least 50% of the diameter. Results: The mean imaging time of coronary MRA was 9.5 ± 4.9 minutes. The prevalence of significant disease on X-ray angiography was 45% (62/138). On a vessel-based analysis, the area under receiver operating characteristic (ROC) curve for the MRA compared with X-ray angiography was 0.90 (95% CI; 0.86 to 0.93). On a patient based analysis, the ROC area was 0.88 (95% CI; 0.81– 0.93). The sensitivity, specificity, positive and negative predictive values of coronary MRA by vessel analysis were 78% (95% CI; 68 – 86%), 86% (82–90%), 60% (51– 69%), 94% (90–96%). These values by patient analysis were 87% (95% CI; 76–94%), 71% (59 – 81%), 71% (59 – 81%), 87% (76–94%). Conclusions: In the current multicenter study using commercial 1.5T MR imagers and sliding partial MIP reconstruction, the diagnostic accuracy of coronary MRA compared to quantitative coronary angiography is good, reflected by an ROC area of 0.88 on patient-based analysis. High negative predictive value indicates that coronary MRA can be used for screening CAD.
Abstract 1351: Ubiquitin Carboxyl-Terminal Esterase L1, Causative Gene of Parkinson’s Disease, Modulates Anti-Inflammatory-Mediated Vascular Remodeling
Authors: Yoichi Takami, Hironori Nakagami, Ryuichi Morishita, Tomohiro Katsuya, Hiromi Rakugi, Yasufumi Kaneda, Toshio Ogihara
Journal: Circulation (2006)

Recent analysis of human genome sequence suggests that multiple gene products regulate tissue development and organ remodeling. The goal of present study was to perform functional screening of a hu...
Brentuximab vedotin: axonal microtubule’s Apollyon
Authors: S Mariotto, S Ferrari, M Sorio, F Benedetti, G Tridente, T Cavallaro, A Gajofatto, S Monaco
Journal: Blood Cancer Journal (2015)

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common side effects encountered in patients treated with chemotherapeutic drugs binding to soluble tubulin or targeting microtubules.1, 2 Some of these drugs, such as taxanes and ixabepilone, stabilize and block microtubule remodeling, whereas others, including Vinca alkaloids, colchicine and eribulin, promote microtubule disassembly.3 Over the last few years, the use of antibody-drug conjugates (ADCs) with potent and highly specific activity against protein targets, which are abundantly expressed on malignant cells, has greatly improved the outcome of patients with cancer. Among ADCs used in patients with hematologic cancer, an anti-CD30 chimeric antibody conjugated by a protease-cleavable dipeptide to monomethyl auristatin E (MMAE; a synthetic agent that blocks polymerization of tubulin), named as brentuximab vedotin (BV), has demonstrated efficacy in the treatment of relapsed or refractory Hodgkin's lymphoma (HL) and systemic anaplastic large-cell lymphoma.4, 5, 6 Neurotoxicity is the greatest concern regarding BV, and the most frequent complication is peripheral neuropathy (PN), which often causes discontinuation of therapy.6, 7, 8, 9, 10, 11 The mechanisms responsible for neuropathy remain unknown, as peripheral nerves do not express CD30, thus apparently precluding the targeted delivery of MMAE to nerve fibers. However, it is unknown whether untargeted or systemic delivery of ADC and/or free MMAE to neuronal bodies and their axonal extensions may occur.12 To date, no studies are available on morphological and ultrastructural changes occurring in peripheral nerves of patients with BV-related PN. Among patients with HL in treatment with BV, who are referred to our clinic for neurological evaluation and electrophysiological investigations, we recently had the opportunity to study a patient with severe neuropathy and to investigate pathological changes at sural nerve biopsy.
Acetylcholine-Provoked Coronary Spasm at Site of Significant Organic Stenosis Predicts Poor Prognosis in Patients With Coronary Vasospastic Angina
Authors: Masanobu Ishii, Koichi Kaikita, Koji Sato, Tomoko Tanaka, Koichi Sugamura, Kenji Sakamoto, Yasuhiro Izumiya, Eiichiro Yamamoto, Kenichi Tsujita, Megumi Yamamuro, Sunao Kojima, Hirofumi Soejima, Seiji Hokimoto, Kunihiko Matsui, Hisao Ogawa
Journal: Journal of the American College of Cardiology (2015)
Prenatal and perinatal risk factors for psychiatric diseases of early onset
Authors: P. Rasanen, H. Hakko, M.-R. Jarvelin, C. M Hultman
Journal: BMJ (1999)

Is there a rationale for rationing chronic dialysis? Two points need clarificationEditor-I agree with Chandna et al that late referral is an important factor in the survival of patients receiving dialysis. 1I am unaware, however, of the source of their information that an NHS consensus statement recommends that nephrology referrals be made at a serum creatinine concentration > 135 mol/l in women and > 180 mol/l in men.The workload generated by this practice would be so enormous that British renal units under present conditions would be unable to cope.I am also concerned that of the authors' 292 patients receiving dialysis, 26 (admittedly high risk) patients spent 44% of their lives in hospital.The costs of inpatient treatment for these high risk patients would be substantially higher than the average cost of £250 a day that the authors quote.