tbuckley/cabot-search huggingface dataset:
Disruption in the temporal sequence of regional ventricular contraction. I. Characteristics and incidence in coronary artery disease.
Authors: B LHolman, JWynne, JIdoine, JNeill
Journal: Circulation (1980)

While spatial asynergy at end-systole has been well characterized in patients with coronary artery disease, assessment of regional asynchrony has been hampered by technical constraints. We developed a computer-assisted method for analyzing regional asynchrony from the equilibrium (ECG-gated) radionuclide ventriculogram. Twenty patients with normal contrast left ventriculograms (nine with a normal coronary arteriogram [group 1] and 11 with coronary artery disease [group 2]) and 20 patients with asynergy during contrast ventriculography (group 3) were studied. The earliest evidence of regional asynchrony occurred in early systole. Regional ejection fraction at one-third systole was 0.32 +/- 0.02 (mean +/- SEM) in group 1, 0.22 +/- 0.01 in group 2 (p less than 0.001) and 0.12 +/- 0.01 in asynergic regions in group 3 patients (p less than 0.001). In group 3, severe forms of regional asynchrony appeared in both early systole and early diastole: five patients (25%) had early systolic paradox, 13 (65%) had regio...
First manifestation of adult-onset Still's disease after COVID-19
Authors: Anna D Bamidis, Philipp Koehler, Veronica di Cristanziano, Kurt Rasche, Baris Demirel, Petra Bacher, Michael Hallek, Matthias Kochanek, Florian Klein, Silke C Hofmann, Ulrich Wesselmann, David M Kofler
Journal: The Lancet Rheumatology (2021)

Adult-onset Still's disease (AOSD) is a rare inflammatory disorder that usually affects young adults, with a bimodal peak at ages 15-25 years and 36-46 years.The disease is characterised by fever of more than 39°C, transient skin rash, leucocytosis, arthralgia, arthritis, or a combination of these symptoms. 1In addition to at least two of the aforementioned major criteria, the Yamaguchi criteria for the diagnosis of AOSD also require the presence of minor criteria-ie, sore throat, lymphadenopathy, hepatomegaly or splenomegaly, abnormal liver function tests, and negative tests for antinuclear antibodies and rheumatoid factor. 1 Infections, malignancies, and other rheumatic diseases need to be excluded.The cytokine interleukin (IL)-1 has a central role in the pathogenesis of AOSD; inhibition of the IL-1 pathway using monoclonal antibodies or IL-1 receptor antagonists significantly ameliorates the disease. 2 IL-1 drives an intense innate immune response by activating neutrophils, macrophages, and mast cells, and by promoting overexpression of several proinflammatory cytokines, including IL-6, IL-8, IL-17, IL-18, and TNF. 3 Viral or bacterial infections have been proposed as potential triggers, but the exact mechanisms underlying AOSD onset remain largely unknown. 4ARS-CoV-2 emerged in late 2019, causing the COVID-19 pandemic.AOSD and COVID-19 share several clinical and laboratory features, including systemic inflam mation, unremitting fever, high serum ferritin, and a potentially life-threatening cytokine release syndrome.Data obtained from single-cell analysis revealed IL-1β-associated inflammasome signa tures and a significant expansion of CD14-positive, IL-1β-positive monocytes in the peripheral blood of patients with severe COVID-19. 5,6Thus, AOSD and the severe immune overreaction which occurs in some patients with COVID-19 might be triggered by the same mechanisms.Here, we report a case of severe AOSD manifestations emerging in a patient suffering from long-term sequelae of COVID-19 for 6 months.In Germany, in March, 2020, a 29-year-old White woman with no notable medical history developed signs of SARS-CoV-2 infection including sore throat, headache, anosmia, ageusia, generalised weakness, shortness of breath, diarrhoea,
The AMA, Tobacco, and the Public Health
Authors: John Simmons
Journal: JAMA (1996)

To the Editor.  —I congratulate you for your hard-hitting issue of July 19, 1995, 1 exposing the  industry's conspiracy to mislead and deceive the American public. As a practicing physician, I am frustrated when I care for a patient with chronic bronchitis, emphysema, or coronary artery disease (to name a few) and then am unable to use an ICD-9-CM  2 to indicate that the illness was caused, in many cases, by tobacco. The only reference to  in the ICD-9-CM is under the category for mental illness, as tobacco addiction 301.5. A precedent exists for including causative agents in defining diseases, for example, alcoholism 313.9, allowing the physician to diagnose alcoholic cirrhosis of the liver 571.2, alcoholic brain syndrome 231.2, or alcoholic cardiomyopathy 225.5.  The same latitude for coding tobacco-related organ damage does not exist in the current ICD-9-CM . Additions to ICD-9-CM could use additional decimals, such as adding
Lysoplasmenylethanolamine accumulation in ischemic/reperfused isolated fatty acid-perfused hearts.
Authors: N JDavies, RSchulz, P MOlley, K DStrynadka, D LPanas, G DLopaschuk
Journal: Circulation Research (1992)

Lysophospholipid accumulation has been implicated in the pathogenesis of irreversible injury during myocardial ischemia and reperfusion. Plasmalogens (phospholipids with a vinyl-ether bond in the sn-1 position) account for more than 50% of total myocardial sarcolemmal and sarcoplasmic reticulum phospholipids. Accumulation of plasmalogen choline and ethanolamine lysophospholipids (lysoplasmenylcholine and lysoplasmenylethanolamine) or the effects of exogenous fatty acids on lysoplasmalogen accumulation during ischemia and reperfusion have not been examined. Isolated working rat hearts perfused with buffer containing either 11 mM glucose or 11 mM glucose plus 1.2 mM palmitate were subjected to aerobic, ischemic, or ischemia/reperfusion protocols. Levels of lysoplasmenylcholine and lysoplasmenylethanolamine were quantified using a two-stage high-performance liquid chromatographic technique. In hearts perfused with glucose alone, no significant differences in levels of lysoplasmenylcholine or lysoplasmenyleth...
Quantification of myocardial perfusion with myocardial contrast echocardiography during left atrial injection of contrast. Implications for venous injection.
Authors: D MSkyba, A RJayaweera, N CGoodman, SIsmail, GCamarano, SKaul
Journal: Circulation (1994)

BACKGROUNDThe purpose of this study was to determine whether myocardial perfusion can be quantified with myocardial contrast echocardiography using left atrial (LA) injection of contrast.METHODS AND RESULTSBased on a series of in vitro and in vivo experiments, the optimal dose of sonicated albumin microbubbles injected into the LA for establishing a linear relation between video intensity and blood volume in the anterior myocardium was determined. In 10 open-chest dogs, myocardial blood flow (MBF) was augmented by increasing myocardial blood volume (MBV) with an intravenous infusion of phenylephrine HCl. In the presence of this drug, left anterior descending artery stenosis was produced, followed by release of stenosis, to change MBF within the anterior myocardium. MBV was calculated by dividing radiolabeled microsphere-derived MBF by microbubble transit rate. There was close coupling between MBF and MBV in the anterior myocardium during LA injection of contrast (y = 1.0x-0.03, SEE = 1.07, r = .92, P < .0...
Steady-state mRNA levels of the sarcolemmal Na(+)-Ca2+ exchanger peak near birth in developing rabbit and rat hearts.
Authors: S RBoerth, D BZimmer, MArtman
Journal: Circulation Research (1994)

To functionally compensate for an underdeveloped sarcoplasmic reticulum in immature cardiomyocytes, it has been proposed that the sarcolemmal Na(+)-Ca2+ exchanger may assume a more predominant role for regulating cytosolic Ca2+. Previous studies using sarcolemma prepared from developing rabbit hearts demonstrated that Na(+)-dependent Ca2+ uptake and exchanger protein content were highest at birth and declined postnatally. To further investigate the significance of the Na(+)-Ca2+ exchanger during normal myocardial development, steady-state mRNA levels of the cardiac Na(+)-Ca2+ exchanger were quantitated by Northern blot and slot-blot analyses using poly(A+) RNA isolated from rabbit and rat ventricles at various fetal and postnatal ages. Northern analyses were performed with a 1.35-kb guinea pig cardiac Na(+)-Ca2+ exchanger cDNA probe. Exchanger mRNA levels were quantitated by densitometric scans of the slot blots, and results were normalized by reprobing the same blots with 32P 5'-end-labeled oligo(dT). In...
The SMC5/6 complex compacts and silences unintegrated HIV-1 DNA and is antagonized by Vpr
Authors: Liane Dupont, Stuart Bloor, James C. Williamson, Sergio Martínez Cuesta, Raven Shah, Ana Teixeira-Silva, Adi Naamati, Edward J.D. Greenwood, Stefan G. Sarafianos, Nicholas J. Matheson, Paul J. Lehner
Journal: Cell Host & Microbe (2021)

Silencing of nuclear DNA is an essential feature of innate immune responses to invading pathogens. Early in infection, unintegrated lentiviral cDNA accumulates in the nucleus yet remains poorly expressed. In HIV-1-like lentiviruses, the Vpr accessory protein enhances unintegrated viral DNA expression, suggesting Vpr antagonizes cellular restriction. We previously showed how Vpr remodels the host proteome, identifying multiple cellular targets. We now screen these using a targeted CRISPR-Cas9 library and identify SMC5-SMC6 complex localization factor 2 (SLF2) as the Vpr target responsible for silencing unintegrated HIV-1. SLF2 recruits the SMC5/6 complex to unintegrated lentiviruses, and depletion of SLF2, or the SMC5/6 complex, increases viral expression. ATAC-seq demonstrates that Vpr-mediated SLF2 depletion increases chromatin accessibility of unintegrated virus, suggesting that the SMC5/6 complex compacts viral chromatin to silence gene expression. This work implicates the SMC5/6 complex in nuclear immunosurveillance of extrachromosomal DNA and defines its targeting by Vpr as an evolutionarily conserved antagonism.
Normal myocardial contractile state in the presence of quinidine.
Authors: WMarkiewicz, RWinkle, GBinetti, RKernoff, D CHarrison
Journal: Circulation (1976)

Since quinidine is one of the few agents available to treat and prevent ventricular arrhythmias in ambulatory patients, its hemodynamic effects have been reevaluated. When given in therapeutic doses to anesthetized mongrel dogs, quinidine significantly reduced heart rate, aortic pressure and flow, but it did not significantly change the first derivative of the left ventricular pressure curve (left ventricular dp/dt) in nine dogs. A subsequent group of dogs was studied after vagotomy and practolol administration to block cardiac reflexes. This group showed significant reductions in heart rate, aortic pressure and left ventricular dp/dt, with the latter returning to predrug control values when preload, afterload and heart rate were maintained constant. These studies suggest that quinidine does not directly affect myocardial contractility when given in therapeutic doses. Furthermore, the reduction in heart rate in these animals provides support for a direct depressant effect of quinidine on the sinus node. T...
Divergent clonal evolution of blastic plasmacytoid dendritic cell neoplasm and chronic myelomonocytic leukemia from a shared TET2-mutated origin
Authors: Kiran Batta, Hasse M. Bossenbroek, Naveen Pemmaraju, Deepti P. Wilks, Richard Chasty, Mike Dennis, Paul Milne, Matthew Collin, Hannah C. Beird, Justin Taylor, Mrinal M. Patnaik, Catherine A. Cargo, Tim C. P. Somervaille, Daniel H. Wiseman
Journal: Leukemia (2021)
Comparative effects of volume loading, dobutamine, and nitroprusside in patients with predominant right ventricular infarction.
Authors: L JDell'Italia, M RStarling, RBlumhardt, J CLasher, R AO'Rourke
Journal: Circulation (1985)

To assess the value of volume loading and to determine the relative efficacy of dobutamine compared with nitroprusside therapy in acute right ventricular infarction (RVMI), 13 patients with clinical, hemodynamic, and radionuclide angiographic evidence of RVMI were evaluated. In 10 patients who had an initial pulmonary arterial wedge pressure less than 18 mm Hg, volume loading did not improve cardiac index (1.9 +/- 0.5 [SD] to 2.1 +/- 0.4 liters/min/m2), despite significant increases in mean right atrial pressure (11 +/- 2 to 15 +/- 2 mm Hg, p less than .001) and pulmonary arterial wedge pressure (10 +/- 4 to 15 +/- 2 mm Hg, p less than .001). Nine patients received dobutamine or nitroprusside in random order, while hemodynamic measurements and radionuclide angiograms were obtained simultaneously. Compared with nitroprusside, dobutamine produced a statistically significant increase in cardiac index (2.0 +/- 0.4 to 2.7 +/- 0.5 vs 2.1 +/- 0.4 to 2.3 +/- 0.5 liters/min/m2, p less than .001), stroke volume ind...
TCTAP A-014 Comparison of TAP Stenting and DK Crush Bifurcation Double Stenting Techniques: Insights from an In Vitro Bench Top Study
Authors: Jaryl Ng, Valeria Paradies, Shengjie Lu, Hwa Liang Leo, Philip Wong, Nicolas Foin, Hui Ying Ang
Journal: Journal of the American College of Cardiology (2021)
Impaired forearm oxygen consumption during static exercise in patients with congestive heart failure.
Authors: JLonghurst, WGifford, RZelis
Journal: Circulation (1976)

In this study, the effects of forearm static exercise were determined on local blood flow and oxygen consumption in 15 normal individuals (NL) and their responses were compared with ten patients in congestive heart failure (CHF). Forearm blood flow was determined by a plethysmographic technique before and during 15% of maximum voluntary contraction of the forearm. Regional arterial and venous oxygen contents were sampled and forearm oxygen consumption calculated by the Fick principle. At rest, forearm blood flow was less in patients with heart failure than in normal individuals; however, this was compensated for by an increased oxygen extraction, thus maintaining forearm oxygen consumption at a normal level. In contrast, during static exercise, forearm blood flow failed to rise normally with heart failure (NL 9.31; CHF 4.35 ml/min-100 ml, P less than 0.001) and the increased oxygen extraction was not sufficient to maintain a normal forearm oxygen consumption (NL .82; CHF .44 ml/min-100 ml, P less than 0.0...
Clinical experience, complications, and survival in 70 patients with the automatic implantable cardioverter/defibrillator.
Authors: D SEcht, KArmstrong, PSchmidt, P EOyer, E BStinson, R AWinkle
Journal: Circulation (1985)

Seventy patients received the automatic implantable defibrillator, five original devices and 72 modified second-generation devices using only bipolar rate sensing and delivering an R wave synchronous cardioverting/defibrillating shock, for either ventricular tachycardia or fibrillation. The primary clinical arrhythmia was sustained ventricular tachycardia in 32 patients, ventricular fibrillation in 20 patients, and both ventricular tachycardia and fibrillation in 18 patients. Before implantation of the device the patients had survived 3.1 +/- 2.3 arrhythmic episodes, including 1.9 +/- 1.7 cardiac arrest, and had received 4.0 +/- 2.1 antiarrhythmic drugs without improvement. Sixty-eight patients ultimately received devices. After a follow-up period of 8.9 +/- 7.7 months (range 1 to 33), 37 patients received a total of 463 discharges. Inability to determine the precise reason for most discharges and the unpleasant nature of the discharges were the major clinical problems encountered. Complications included ...
Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease.
Authors: M RMalinow, S SKang, L MTaylor, P WWong, BCoull, TInahara, DMukerjee, GSexton, BUpson
Journal: Circulation (1989)

A micromethod adapted for automated determinations was used to measure basal plasma levels of homocyst(e)ine [H(e)]. These levels included the sum of free and bound forms of homocysteine, its disulfide oxidation product, homocystine, and the homocysteine-cysteine-mixed disulfide. Two groups of subjects were studied: apparently healthy individuals (n = 103) and patients with peripheral arterial occlusive disease (PAOD) (n = 47). Because age in PAOD patients was higher than in control subjects, the control subjects were subdivided into younger and older groups (aged 60 years or less and more than 60 years, respectively). The H(e) levels in the younger groups were 11.18 +/- 3.58 (mean +/- SD, expressed as homocysteine) and 8.58 +/- 2.82 nmol/ml in men and women, respectively; in the older groups, the levels were 10.74 +/- 2.16 and 9.04 +/- 2.16 nmol/ml in men and women, respectively. There was a positive correlation of H(e) levels with age in the younger control women (r = 0.373; p less than 0.02); no signif...
Change in (dP/dt)max as an index of myocardial microvascular permeability.
Authors: G ALaine
Journal: Circulation Research (1987)

We frequently study processes that alter microvascular permeability in the heart. Myocardial microvascular permeability has been estimated by determining the filtration independent reflection coefficient for beta-lipoprotein (sigma beta-LIPO). This technique requires the measurement of myocardial lymph flow rate and the lymph-to-plasma protein concentration ratio. Unfortunately, it is a nonsurvival procedure. An index of myocardial microvascular permeability was needed that could be determined in experimental preparations without sacrificing valuable chronically instrumented animals. We attempted to relate changes in myocardial microvascular permeability and myocardial edema formation to some index of myocardial performance. In 33 acute, anesthetized dogs (with normal or disrupted myocardial microvasculatures), we measured systemic arterial pressure, systemic venous pressure, coronary sinus pressure, left ventricular pressure, the maximum rate of change in left ventricular pressure (dP/dt)max, myocardial ...
Oxygen Supplementation Among Patients in the Intensive Care Unit
Authors: Massimo Girardis, Stefano Busani
Journal: JAMA (2017)

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Learning Curve for Gastric Endoscopic Submucosal Dissection – Where are we?
Authors: S Silva Mendes, A Ferreira, R Costa, T Leal, AC Caetano, R Gonçalves
Journal: Endoscopy (2021)

Aims Endoscopic submucosal dissection (ESD) is a technique for the resection of early malignant gastric lesions under implementation in Western countries. This study intends to characterize the learning curve for this technique to facilitate the development of training programs.
The risk of malignancy in patients with secukinumab‐treated psoriasis, psoriatic arthritis and ankylosing spondylitis: analysis of clinical trial and postmarketing surveillance data with up to five years of follow‐up
Authors: M. Lebwohl, A. Deodhar, C.E.M. Griffiths, M.A. Menter, D. Poddubnyy, W. Bao, V. Jehl, K. Marfo, P. Primatesta, A. Shete, V. Trivedi, P.J. Mease
Journal: British Journal of Dermatology (2021)

Data on the use of biologic therapy and malignancy risk are inconsistent due to limited long-term robust studies.To assess the malignancy risk in patients with secukinumab-treated psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS).This integrated safety analysis from both the secukinumab clinical trial programme and postmarketing safety surveillance data included any patient receiving at least one approved dose of secukinumab with a maximum of 5 years of follow-up. Safety analyses evaluated the rate of malignancy using exposure-adjusted incidence rates [EAIR; incidence rates per 100 patient treatment-years (PTY)]. Standardized incidence ratios (SIRs) were reported using the Surveillance, Epidemiology, and End Results Program (SEER) database as a reference population. Crude incidence of malignancy was also reported using postmarketing surveillance data.Safety data from 49 clinical trials with secukinumab-treated patients were included: 10 685 patients with psoriasis, 2523 with PsA and 1311 with AS. Across indications over a 5-year period, the EAIR of malignancy was 0·85 per 100 PTY [95% confidence interval (CI) 0·74-0·98] in secukinumab-treated patients, corresponding to 204 patients per 23 908 PTY. Overall, the observed vs. expected number of malignancies from secukinumab clinical trial data were comparable, as indicated by an SIR of 0·99 (95% CI 0·82-1·19) across indications. The estimated crude cumulative incidence reporting rate per 100 PTY for malignancy was 0·27 in the postmarketing surveillance data across indications with a cumulative exposure of 285 811 PTY.In this large safety analysis, the risk of malignancy was low for up to 5 years of secukinumab treatment. These data support the long-term use of secukinumab in these indications.
POT1 Regulates Proliferation and Confers Sexual Dimorphism in Glioma
Authors: Ali Jalali, Kwanha Yu, Vivek Beechar, Navish A. Bosquez Huerta, Anthony Grichuk, Deepika Mehra, Brittney Lozzi, Kathleen Kong, Kenneth L. Scott, Ganesh Rao, Matthew N. Bainbridge, Melissa L. Bondy, Benjamin Deneen
Journal: Cancer Research (2021)

Abstract Germline POT1 mutations are found in a spectrum of cancers and confer increased risk. Recently, we identified a series of novel germline POT1 mutations that predispose carrier families to the development of glioma. Despite these strong associations, how these glioma-associated POT1 mutations contribute to glioma tumorigenesis remains undefined. Here we show that POT1-G95C increases proliferation in glioma-initiating cells in vitro and in progenitor populations in the developing brain. In a native mouse model of glioma, loss of Pot1a/b resulted in decreased survival in females compared with males. These findings were corroborated in human glioma, where low POT1 expression correlated with decreased survival in females. Transcriptomic and IHC profiling of Pot1a/b-deficient glioma revealed that tumors in females exhibited decreased expression of immune markers and increased expression of cell-cycle signatures. Similar sex-dependent trends were observed in human gliomas that had low expression of POT1. Together, our studies demonstrate context-dependent functions for POT1 mutation or loss in driving progenitor proliferation in the developing brain and sexual dimorphism in glioma. Significance: This study shows that manipulation of POT1 expression in glioma has sex-specific effects on tumorigenesis and associated immune signatures.
Hypervascular Pancreatic Lesions on Contrast-Enhanced EUS: Beyond Neuroendocrine Tumors
Authors: IM Cazacu, IF Cherciu Harbiyeli, A Constantin, C Copaescu, V Tomulescu, N Bejinariu, V Surlin, C Stroescu, C Popescu, A Saftoiu
Journal: Endoscopy (2021)

Aims Although pancreatic neuroendocrine tumors (PNETs) typically have a solid, hypervascular appearance on contrast-enhanced endoscopic ultrasound (CE-EUS), other non-PNET lesions may have a similar appearance. It is important to discriminate hypervascular pancreatic lesions because of different treatment option and prognosis. With this background, we decided to review our single-center experience with regard to hypervascular pancreatic lesions on CE-EUS.