tbuckley/cabot-search huggingface dataset:
Gout: why is this curable disease so seldom cured?
Authors: Swan Sim Yeap, Suk Chyn Gun
Journal: Annals of the Rheumatic Diseases (2013)

We read with interest the article by Doherty et al 1 in which they lament the suboptimal care of patients with gout, as the majority are managed by non-specialists. In 2005, we had surveyed non-rheumatologists on their practices regarding the management of gout.2 Of the 128 respondents, 52.3% were general practitioners (GPs). A significant proportion of respondents were treating gout suboptimally; 50% would stop allopurinol during an acute attack, once allopurinol was started, only 54.7% would continue indefinitely and 15% would treat asymptomatic hyperuricaemia. As a result of this, in October 2008, the Malaysian Society of Rheumatology and Ministry of Health, …
Left ventricular failure induced by long-term hypertension in rats.
Authors: J MCapasso, TPalackal, GOlivetti, PAnversa
Journal: Circulation Research (1990)

To determine whether the duration of hypertension is an essential component in the evolution of myocardial dysfunction, renal artery constriction was performed in male Fischer 344 rats at 4 months of age, and in vivo global cardiac performance of sham-operated and experimental animals was evaluated 8 months later. Systemic arterial blood pressure increased to 173 +/- 5 mm Hg 2 weeks after the arteries were clipped and remained elevated for the following 5 months. Blood pressure decreased over the remaining 3 months to a value not significantly different from control rats that were killed, 132 +/- 4 mm Hg. After 8 months of renovascular hypertension, we observed that the elevated level of systolic arterial pressure was accompanied by a distinct absence of left ventricular hypertrophy when measured at the ventricular weight level. Moreover, left ventricular end-diastolic pressure increased in hypertensive animals from 6.0 to 24.0 mm Hg while peak left ventricular pressure was identical to controls. In addit...
Adenosine release and high energy phosphates in intact dog hearts during norepinephrine infusion.
Authors: M WGorman, X HNing, M XHe, M APortman, H VSparks
Journal: Circulation Research (1992)

Cardiac adenosine release is thought to depend on the oxygen supply/demand ratio, and this effect may be mediated by changes in high energy phosphate concentrations. Previous studies supporting this hypothesis have been done primarily in isolated hearts. We tested this hypothesis in intact dog hearts. Anesthetized, open-chest dogs were placed in a 4.7-T magnet where 31P nuclear magnetic resonance spectra were acquired via a surface coil over the heart at 2-minute intervals (60 scans, 2-second interpulse delay). Coronary sinus flow was shunted through a flow probe and returned via a jugular vein. After a control period, intracoronary norepinephrine was infused (12 micrograms/min) for 16 minutes and plasma samples were taken every 5 minutes. The phosphocreatine/ATP peak area ratio was used as an index of high energy phosphate changes. During norepinephrine infusion, arterial pressure, heart rate, coronary sinus flow, oxygen consumption, and adenosine release all increased significantly. Adenosine release pe...
Third-Space Approach Vs Flexible Endoscopic Septotomy For The Treatment Of Short-Septum Zenker’s Diverticulum
Authors: R Maselli, M Spadaccini, A Fugazza, E Vespa, PA Galtieri, G Pellegatta, EC Ferrara, S Carrara, A Anderloni, A Repici
Journal: Endoscopy (2021)

Aims Flexible endoscopic septotomy (FES) has been reported as a safe and effective treatment for Zenker’s diverticulum (ZD). However, patients with short septum (ss;≤20mm) ZD still represent a difficult-to-treat subgroup of patients because of the anatomical limitation leading to reduced operating space for both rigid and flexible endoscopic treatments. Recently, third space tunneling approaches, namely Z-POEM and POES,have been developed to allow a safer,more complete myotomy; however, comparison data the standard flexible septotomy are still lacking. This is a retrospective analysis, comparing efficacy and safety between septotomy performed by a luminal or a third space approach (POES) for treating ssZD.
Characterization of the vascular thromboxane A2/prostaglandin endoperoxide receptor in rabbit aorta. Regulation by dexamethasone.
Authors: W CSessa, P VHalushka, AOkwu, ANasjletti
Journal: Circulation Research (1990)

Recently, we have shown that dexamethasone treatment of rabbits specifically reduces vascular smooth muscle responsiveness to agonists that interact with the vascular thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptor. One potential site at which dexamethasone can influence prostanoid-mediated vasoconstriction may be at the level of the vascular TXA2/PGH2 receptor. Therefore, we characterized the vascular TXA2/PGH2 receptor in rabbit aortic membranes and examined the influence of dexamethasone treatment on vascular TXA2/PGH2 receptor affinity and number. The binding of [125I][1S-(1 alpha,2 beta(5Z),3 alpha(1E,3R)4 alpha)]-7-[3-(3- hydroxy-4-(p-iodophenoxy)-1-butenyl)-7-oxabicyclo[2.2.1] heptan-2-yl]-5-heptanoic acid ([125I]BOP), a potent TXA2/PGH2 receptor agonist, to rabbit aortic membranes was saturable, displaceable, and dependent on protein concentration. Scatchard analysis of equilibrium binding data disclosed one class of high affinity binding sites with a Kd of 0.44 +/- 0.13 nM and a Bmax of 114....
Distribution of coronary artery disease. Prediction by echocardiography.
Authors: A CDortimer, R LDeJoseph, R AShiroff, A JLiedtke, RZelis
Journal: Circulation (1976)

To assess the sensitivity of standard echocardiography in detecting ventricular motion abnormalities in patients with coronary artery disease (CAD) without prior myocardial infarction, 56 consecutive patients with a history of angina pectoris were studied during an angina-free period. In the 48 patients with adequate echocardiograms, the amplitude of septal and posterior wall motion in the high, mid, and low left ventricle was determined and used to predict prospectively in a blinded fashion the sites of angiographically-determined CAD. Twenty-eight of 35 patients (80%) with disease of the left anterior descending artery (LAD) had diminished interventricular septal motion (P less than 0.001) and 14 of 27 patients (52%) with disease of posterior vessels had diminished posterior wall motion on echocardiogram. When abnormalties of echocardiographic wall motion were compared with left ventriculography, the results were similar. Echocardiography may aid in predicting the presence and distribution of CAD, espec...
The Heart: Arteries and Veins
Authors: E. William Hancock
Journal: JAMA (1986)

One of the premiere large textbooks of cardiology, this book was first published in 1966 and last revised in 1982. The immense success and popularity of this book will certainly continue. The new edition has 8% more pages, 12% more authors, and 27% more chapters. There are now seven editors and 183 authors of this encyclopedic work. The most visible additions to the volume are 18 new chapters about specific techniques and procedures in cardiology, covering topics such as thrombolytic therapy, laser angioplasty, total mechanical heart, esophageal electrocardiography, signal averaged electrocardiography, the internal defibrillator, Doppler ultrasound, computed tomography, digital subtraction angiography, magnetic resonance imaging, and others. There is also a new section about clinical pharmacology, with eight new chapters covering commonly used cardiovascular drugs. The new chapters about drugs and procedures add 272 new pages to part VII, which now constitutes 25% of the volume compared with 12% in the
The Authors Reply
Authors: Yan Xie
Journal: Kidney International (2017)

Thank you for commenting on our work.1Kamal F. Khan M.A. Howden C.W. Proton pump inhibitors and chronic kidney disease.Kidney Int. 2017; 92: 515Abstract Full Text Full Text PDF Scopus (2) Google Scholar Exposure to proton pump inhibitors (PPIs) is associated with increased risk of chronic kidney disease with and without intervening acute kidney injury.2Xie Y. Bowe B. Li T. et al.Proton pump inhibitors and risk of incident CKD and progression to ESRD.J Am Soc Nephrol. 2016; 27: 3153-3163Crossref PubMed Scopus (213) Google Scholar, 3Xie Y. Bowe B. Li T. et al.Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury.Kidney Int. 2017; 91: 1482-1494Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar In their letter to the editor, Kamal and colleagues reiterate some of the limitations highlighted in our Discussion. They also elaborate on the limitations of using prescription records to classify exposure to PPIs that are also available over the counter. We defined drug exposure according to prescription records, and it is possible that some cohort participants may have used over-the-counter PPIs; the potential misclassification of exposure (although unlikely as explained in our Discussion) would have resulted in underestimation of risk and biased the results toward the null hypothesis. The body of evidence suggests a significant association between PPI use and risk of kidney outcomes; both the precautionary principle and the Hippocratic principle of “primum non nocere” suggest that the burden of proof lies with the demonstration that PPIs are not harmful to the kidney. We vigorously encourage the development of randomized controlled trials to address this matter. Proton pump inhibitors and chronic kidney diseaseKidney InternationalVol. 92Issue 2PreviewIn their recent population cohort study using the Department of Veterans Affairs databases, Xie et al.1 evaluated a possible association between proton pump inhibitor (PPI) use and chronic kidney disease. They concluded that PPI use is an independent risk factor for the development of chronic kidney disease in the absence of prior acute kidney injury. However, limitations of the study design should be considered. The authors adjusted for hemoglobin A1C, cardiovascular disease, chronic lung disease, and use of angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs. Full-Text PDF Open Archive
Emergency revascularization for unstable angina.
Authors: L AGolding, F DLoop, W CSheldon, P CTaylor, L KGroves, D MCosgrove
Journal: Circulation (1978)

Emergency revascularization for unstable angina (defined according to criteria of the National Cooperative Study Group) was performed in 100 consecutive patients. The mean interval from onset of pain to operation was one day. Nineteen patients had single-vessel narrowing of greater than 70% of lumen diameter, 32 double-vessel obstruction and 49 triple-vessel disease. Fourteen of these patients had left main trunk obstruction. Four patients died within 30 days, three from complications of myocardial infarction. Seventeen of 96 (18%) early survivors sustained perioperative infarction. After a mean follow-up of 42 months, four late deaths and three late infarctions occurred. Postoperative angiography in 47 patients (mean interval 14 months) showed 86% graft patency. Of 92 survivors, 72 are symptom-free. Three of the four operative deaths occurred within 24 hours postoperatively; in each of these, postmortem examination confirmed a recent myocardial infarction which antedated the operation, despite the absenc...
Inhibition by carotid baroreflex of exercise-induced increases in arterial pressure.
Authors: S CWalgenbach, D EDonald
Journal: Circulation Research (1983)

Mean arterial blood pressure, heart rate, and cardiac output were measured during continuous graded exercise (5.5 km/hr; 0, 7, 14, and 21% grades) in conscious dogs, under each of the following four conditions: (1) baroreceptors intact, (2) chronic aortic arch denervation, (3) chronic aortic arch denervation and surgical preparation of the carotid sinuses for later reversible vascular isolation, and (4) chronic aortic arch denervation and carotid sinuses vascularly isolated at a fixed pressure. Arterial blood pressure increased with increasing work load to a maximum of 12 +/- 3, 18 +/- 5, and 14 +/- 5 mm Hg above control in conditions 1, 2, and 3, respectively. In condition 4, the maximum increase in pressure during graded exercise was 51 +/- 7 mm Hg above control. Upon cessation of graded exercise, the increase in arterial pressure persisted through the 5-minute recovery period. Heart rate and cardiac output increased similarly in proportion to work load under all four conditions. In contrast to dogs in ...
Significance of quiescent smooth muscle migration in the injured rat carotid artery.
Authors: A WClowes, S MSchwartz
Journal: Circulation Research (1985)

Cellular accumulation in the intima of injured artery has generally been attributed to smooth muscle cell proliferation. Since smooth muscle cells in normal artery are found mainly in the media, migration of smooth muscle cells into the intima has been considered a necessary prerequisite for subsequent myointimal thickening. The nondividing medial cells would appear to have no role in the reparative process. We have investigated in the rat ballooned carotid the possibility that nondividing cells might also contribute to injury-induced intimal thickening. All proliferating smooth muscle cells were labeled by 3H-thymidine given by continuous intraperitoneal infusion. The amounts of 3H-thymidine used were not toxic and did not inhibit smooth muscle cell proliferation. Autoradiograms performed on histological cross-sections showed a progressive decrease in the fraction of unlabeled cells at 3, 7, and 14 days after carotid injury. However, the actual number of nondividing cells remained constant. The calculate...
Abstract 12620: Effect of Sacubitril-valsartan on the Incidence Arrhythmias in Patients With Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta Analysis
Authors: Edgar E Acuna Morin, Jennifer Maning, Sunita Mahabir, Mariana Ramirez, Sandra Chaparro
Journal: Circulation (2020)

Introduction: Sacubitril-Valsartan (ARNI) has known mortality benefit in patients with HFrEF. Nevertheless, little is known of its influence on arrhythmias. The purpose of this study was to investigate its net effect on the incidence of arrhythmias in patients with HFrEF through a systematic review and meta-analysis of published literature. Methods: We searched Medline, Embase &amp; the Cochrane library through April 15th, 2020 for studies including patients with EF 40% or lower treated with ACEI or ARB and transitioned to ARNI, reporting the incidence of any arrhythmias or ICD shocks in patients with either an ICD, CRT, pacemaker or loop recorder. The primary outcome was the incidence of sustained VT, while the secondary outcomes were the incidence of nonsustained VT (NSVT), appropriate ICD shocks, biventricular pacing (BiV-pacing) in patients with CRT, and episodes of atrial tachycardia or fibrillation (AT/AF) &gt; 30 seconds. The Newcastle-Ottawa tool was used to assess studies. A random-effects meta-analysis was performed using pooled proportions and heterogeneity was examined using I2 statistics. Statistical analyses were carried out using Review Manager 5.3 by Cochrane. Results: 330 subjects were pooled from three studies (two retrospective and one prospective). Mean age was 68±9.7. 79% were males. 74% had ischemic cardiomyopathy. Mean EF was 29% and mean NYHA Class was 2.4. ICD was implanted in 51%, of whom 44% had CRT. Mean follow-up time was 11±1.7 months. The odds ratio (OR) for sustained VT, was 0.59 ( p=0.08 ). For NSVT was 0.65 ( p=0.008* ), appropriate ICD shocks 0.59 ( p=0.09 ), BiV-pacing 2.59 ( p=&lt;0.00001* ), and for episodes of AT/AF &gt; 30s. 0.62 ( p=0.03* ). All in favor of ARNI. Conclusions: This meta-analysis demonstrates that in patients with HFrEF who transition from ACEI or ARB to ARNI, there is a tendency of decreasing ventricular &amp; atrial arrhythmias, appropriate ICD shocks, as well as tendency towards increasing BiV-pacing in patients with CRT.
The evolving landscape of N6-methyladenosine modification in the tumor microenvironment
Authors: Yunru Gu, Xi Wu, Jingxin Zhang, Yuan Fang, Yutian Pan, Yongqian Shu, Pei Ma
Journal: Molecular Therapy (2021)

The tumor microenvironment (TME), controlled by intrinsic mechanisms of carcinogenesis and epigenetic modifications, has, in recent years, become a heavily researched topic. The TME can be described in terms of hypoxia, metabolic dysregulation, immune escape, and chronic inflammation. RNA methylation, an epigenetic modification, has recently been found to have a pivotal role in shaping the TME. The N6-methylation of adenosine (m6A) modification is the most common type of RNA methylation that occurs in the N6-position of adenosine, which is the primary internal modification of eukaryotic mRNA. Compelling evidence has demonstrated that m6A regulates transcriptional and protein expression through splicing, translation, degradation, and export, thereby mediating the biological processes of cancer cells and/or stromal cells and characterizing the TME. The TME also has a crucial role in the complicated regulatory network of m6A modifications and, subsequently, influences tumor initiation, progression, and therapy responses. In this review, we describe the features of the TME and how the m6A modification modulates and interacts with it. We also focus on various factors and pathways involved in m6A methylation. Finally, we discuss potential therapeutic strategies and prognostic biomarkers with respect to the TME and m6A modification. The tumor microenvironment (TME), controlled by intrinsic mechanisms of carcinogenesis and epigenetic modifications, has, in recent years, become a heavily researched topic. The TME can be described in terms of hypoxia, metabolic dysregulation, immune escape, and chronic inflammation. RNA methylation, an epigenetic modification, has recently been found to have a pivotal role in shaping the TME. The N6-methylation of adenosine (m6A) modification is the most common type of RNA methylation that occurs in the N6-position of adenosine, which is the primary internal modification of eukaryotic mRNA. Compelling evidence has demonstrated that m6A regulates transcriptional and protein expression through splicing, translation, degradation, and export, thereby mediating the biological processes of cancer cells and/or stromal cells and characterizing the TME. The TME also has a crucial role in the complicated regulatory network of m6A modifications and, subsequently, influences tumor initiation, progression, and therapy responses. In this review, we describe the features of the TME and how the m6A modification modulates and interacts with it. We also focus on various factors and pathways involved in m6A methylation. Finally, we discuss potential therapeutic strategies and prognostic biomarkers with respect to the TME and m6A modification.
Microwave ablation induces Th1-type immune response with activation of ICOS pathway in early-stage breast cancer
Authors: Wenbin Zhou, Muxin Yu, Hong Pan, Wen Qiu, Hui Wang, Mengjia Qian, Nan Che, Kai Zhang, Xinrui Mao, Li Li, Ruoxi Wang, Hui Xie, Lijun Ling, Yi Zhao, Xiaoan Liu, Cong Wang, Qiang Ding, Shui Wang
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Despite great advances in the treatment of breast cancer, innovative approaches are still needed to reduce metastasis. As a minimally invasive local therapy (not standard therapy for breast cancer), microwave ablation (MWA) has been attempted to treat breast cancer, but the local effect and immune response induced by MWA have seldom been reported. Methods The clinical study was performed to determine the complete ablation rate of MWA for early-stage breast cancer. Secondary endpoints included safety and antitumor immune response. 35 subjects from this clinical study were enrolled in the current report, and the local effect was determined by pathological examinations or follow-up. To investigate MWA-induced immune response, patients treated with surgery (n=13) were enrolled as control, and blood samples were collected before and after MWA or surgery. The immune cell populations, serum cytokines, secretory immune checkpoint molecules, and T-cell receptor sequencing were analyzed. Results Of 35 enrolled patients, 32 (91.4%) showed complete ablation. Compared with surgery, MWA induced significantly increased levels of inducible co-stimulator (ICOS)+ activated CD4+ T cells and serum interferon gamma, indicating a shift in the Th1/Th2 balance toward Th1. The activated ICOS pathway was involved in the MWA-induced adaptive immune response. T-cell receptor sequencing revealed MWA of primary tumor activated T lymphocytes expansion and recognized some cancer-specific antigens. Moreover, CD4+ effector memory T-cell response was induced by MWA, and the immune response still existed after surgical resection of the ablated tumor. Conclusions MWA may not only be a promising local therapy but also a trigger of antitumor immunity for breast cancer, opening new avenues for the treatment of breast cancer. Combinatorial strategy using additional agents which boost MWA-induced immune response could be considered as potential treatment for clinical study for early breast cancer therapy.
Hypoxia-inducible factor activity promotes antitumor effector function and tissue residency by CD8+ T cells
Authors: Ilkka Liikanen, Colette Lauhan, Sara Quon, Kyla Omilusik, Anthony T. Phan, Laura Barceló Bartrolí, Amir Ferry, John Goulding, Joyce Chen, James P. Scott-Browne, Jason T. Yustein, Nicole E. Scharping, Deborah A. Witherden, Ananda W. Goldrath
Journal: Journal of Clinical Investigation (2021)

Adoptive T cell therapies (ACTs) hold great promise in cancer treatment, but low overall response rates in patients with solid tumors underscore remaining challenges in realizing the potential of this cellular immunotherapy approach. Promoting CD8+ T cell adaptation to tissue residency represents an underutilized but promising strategy to improve tumor-infiltrating lymphocyte (TIL) function. Here, we report that deletion of the HIF negative regulator von Hippel-Lindau (VHL) in CD8+ T cells induced HIF-1α/HIF-2α-dependent differentiation of tissue-resident memory-like (Trm-like) TILs in mouse models of malignancy. VHL-deficient TILs accumulated in tumors and exhibited a core Trm signature despite an exhaustion-associated phenotype, which led to retained polyfunctionality and response to αPD-1 immunotherapy, resulting in tumor eradication and protective tissue-resident memory. VHL deficiency similarly facilitated enhanced accumulation of chimeric antigen receptor (CAR) T cells with a Trm-like phenotype in tumors. Thus, HIF activity in CD8+ TILs promotes accumulation and antitumor activity, providing a new strategy to enhance the efficacy of ACTs.
Evidence from a nonrandomized study that coronary surgery prolongs survival in patients with two-vessel coronary disease.
Authors: K EHammermeister, T ADeRouen, H TDodge
Journal: Circulation (1979)

Within the larger Seattle Heart Watch arteriography registry, surgically treated patients non randomly selected for direct myocardial revascularization were matched to medically treated patients such that each of the 287 pairs was identical in seven variables (ejection fraction, ventricular arrhythmia on resting electrocardiogram, age, heart murmur, stenosis of left main coronary artery greater than or equal to 50%, number of vessels with stenosis greater than or equal to 70%, and use of diuretics) previously demonstrated to be independently predictive of survival. Actuarial survival analyses based on cardiovascular deaths (average follow-up 3.5 years) indicate improved survival for the entire surgical matched pair cohort (p = 0.008) and for the surgically treated subgroup with two-vessel disease (p = 0.0002) when compared to the medical cohort. These results were confirmed by examination of the entire arteriography registry (n = 1524) in which these seven variables were known, using Cox's model for survi...