tbuckley/cabot-search huggingface dataset:
Inhibition of the mTORC Pathway in the Antiphospholipid Syndrome
Authors: Steven Van Laecke, Evi V Nagler, Raymond Vanholder
Journal: New England Journal of Medicine (2014)

Inhibition of the mTORC Pathway in the Antiphospholipid SyndromeTo the Editor: Canaud et al. (July 24 issue) 1 describe the activation of the mammalian target of rapamycin complex (mTORC) through the phosphatidyl-inositol 3-kinase (PI3K)-AKT pathway in patients with the antiphospholipid syndrome, leading to chronic vascular lesions.In their retrospective analysis of 37 kidney-transplant recipients with the antiphospholipid syndrome, 10 patients who were treated with mTOR inhibitors had better graft survival, in line with in vitro studies.Since patients with catastrophic antiphospholipid syndrome have analogous vascular alterations, perhaps mTOR inhibitors could prevent vasculopathy in the antiphospholipid syndrome.However, venous thrombosis remains the most common thrombotic manifestation of the antiphospholipid syndrome, and mounting evidence suggests that mTOR inhibitors are prothrombogenic. 2Serum concentrations of von Willebrand factor were higher in kidney-transplant recipients who were treated with mTOR inhibitors 2 and in patients with the antiphospholipid syndrome. 3Among patients who were treated with mTOR inhibitors, as compared with those who did not receive mTOR inhibitors, the risk of thromboembolism was higher among kidney-transplant recipients (adjusted odds ratio, 3.0; 95% confidence interval, 1.3 to 7.0) 4 and among lung-transplant recipients. 5 We think an increased risk of thrombosis may offset the possible benefit of mTOR inhibitors among patients with the antiphospholipid syndrome.
Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension.
Authors: PVerdecchia, GSchillaci, MGuerrieri, CGatteschi, GBenemio, FBoldrini, CPorcellati
Journal: Circulation (1990)

The effects of circadian blood pressure (BP) changes on the echocardiographic parameters of left ventricular (LV) hypertrophy were investigated in 235 consecutive subjects (137 unselected untreated patients with essential hypertension and 98 healthy normotensive subjects) who underwent 24-hour noninvasive ambulatory blood pressure monitoring (ABPM) and cross-sectional and M-mode echocardiography. In the hypertensive group, LV mass index correlated with nighttime (8:00 PM to 6:00 AM) systolic (r = 0.51) and diastolic (r = 0.35) blood pressure more closely than with daytime (6:00 AM to 8:00 PM) systolic (r = 0.38) and diastolic (r = 0.20) BP, or with casual systolic (r = 0.33) and diastolic (r = 0.27) BP. Hypertensive patients were divided into two groups by presence (group 1) and absence (group 2) of a reduction of both systolic and diastolic BP during the night by an average of more than 10% of the daytime pressure. Casual BP, ambulatory daytime systolic and diastolic BP, sex, body surface area, duration ...
Linked electronic health records for research on a nationwide cohort of more than 54 million people in England: data resource
Authors: Angela Wood, Rachel Denholm, Sam Hollings, Jennifer Cooper, Samantha Ip, Venexia Walker, Spiros Denaxas, Ashley Akbari, Amitava Banerjee, William Whiteley, Alvina Lai, Jonathan Sterne, Cathie Sudlow
Journal: BMJ (2021)

Abstract Objective To describe a novel England-wide electronic health record (EHR) resource enabling whole population research on covid-19 and cardiovascular disease while ensuring data security and privacy and maintaining public trust. Design Data resource comprising linked person level records from national healthcare settings for the English population, accessible within NHS Digital’s new trusted research environment. Setting EHRs from primary care, hospital episodes, death registry, covid-19 laboratory test results, and community dispensing data, with further enrichment planned from specialist intensive care, cardiovascular, and covid-19 vaccination data. Participants 54.4 million people alive on 1 January 2020 and registered with an NHS general practitioner in England. Main outcome measures Confirmed and suspected covid-19 diagnoses, exemplar cardiovascular conditions (incident stroke or transient ischaemic attack and incident myocardial infarction) and all cause mortality between 1 January and 31 October 2020. Results The linked cohort includes more than 96% of the English population. By combining person level data across national healthcare settings, data on age, sex, and ethnicity are complete for around 95% of the population. Among 53.3 million people with no previous diagnosis of stroke or transient ischaemic attack, 98 721 had a first ever incident stroke or transient ischaemic attack between 1 January and 31 October 2020, of which 30% were recorded only in primary care and 4% only in death registry records. Among 53.2 million people with no previous diagnosis of myocardial infarction, 62 966 had an incident myocardial infarction during follow-up, of which 8% were recorded only in primary care and 12% only in death registry records. A total of 959 470 people had a confirmed or suspected covid-19 diagnosis (714 162 in primary care data, 126 349 in hospital admission records, 776 503 in covid-19 laboratory test data, and 50 504 in death registry records). Although 58% of these were recorded in both primary care and covid-19 laboratory test data, 15% and 18%, respectively, were recorded in only one. Conclusions This population-wide resource shows the importance of linking person level data across health settings to maximise completeness of key characteristics and to ascertain cardiovascular events and covid-19 diagnoses. Although this resource was initially established to support research on covid-19 and cardiovascular disease to benefit clinical care and public health and to inform healthcare policy, it can broaden further to enable a wide range of research.
Planetary healthy publics after COVID-19
Authors: Stephen Hinchliffe, Lenore Manderson, Martin Moore
Journal: The Lancet Planetary Health (2021)

COVID-19 is a sign of a global malaise. The pandemic is an outcome of what we term a planetary dysbiosis, for which underlining drivers include inequality and the exploitation and extraction of human and non-human labours. The implication is that the usual fixes to outbreaks of infectious diseases (ie, surveillance, pharmaceutical measures, and non-pharmaceutical measures) will be insufficient without a thorough reappraisal of and investment in planetary health. Given the heterogeneity and diversity of environments and populations, we envisage these actions as a matter for the generation of new kinds of public, requiring widespread and multiple forms of engagement to generate lasting solutions. We use and extend the concept of healthy publics to suggest a movement that can start to reclaim planetary health as a collective and ongoing issue.
From the authors
Authors: P. P. Walker, L. Davies
Journal: European Respiratory Journal (2007)

<b>Background: </b>Exposure to household air pollution (HAP) is associated with respiratory health problems in low and middle income countries. The aim of this study was to assess the association between respiratory symptoms and exposure to wood smoke in rural area of Nepal. <b>Methods: </b>A cross-sectional study of adults (16+ years) in a rural population (n=846) exposed to wood smoke and a non-exposed urban population (n=802) in Nepal. Validated questionnaire including that of respiratory symptoms, spirometry data were acquired along with indoor air quality (PM<sub>2.5</sub> and CO) and outdoor PM<sub>2.5</sub> measurement. <b>Results: </b>Rural females were significantly more likely to complain of ever having wheezed (32.8 % vs. 23.8%; p&lt;0.001) compared to their male counterparts with smoking being a major risk factor. Women exposed to HAP were more likely to complain of dyspnoea not induced by exercise (OR=3.3, 95% CI 1.46-7.57), dyspnoea with wheeze (4.91, 2.49-9.69), ever wheeze (4.62, 2.71-7.87) and chest tightness (3.18, 1.53-6.61) but were not more likely to complain of productive cough. 24-hour PM<sub>2.5</sub> measurement was positively associated with breathlessness and wheeze in women. Urban males exposed to outdoor air pollution were more likely to report ever wheeze (3.06, 1.28-7.31) and wheeze on most days and night (3.30, 1.35-8.13). There was a high negative correlation between lung function indices (FEV<sub>1</sub>, FEF<sub>25-75</sub> and FEV<sub>1</sub>/FVC) and the presence of respiratory symptoms in those exposed to HAP. <b>Conclusion: </b>The study suggests that women exposed to HAP reported more respiratory symptoms but males exposed to outdoor air pollution not HAP reported more symptoms.
Effect of wall shear rate on thrombogenesis in microvessels of the rat mesentery.
Authors: MSato, NOhshima
Journal: Circulation Research (1990)

The role of hemodynamics on platelet thrombus formation was studied in venules and arterioles of the rat mesentery. Thrombus formation was induced by the fluorescent dye/light method for examination of the following factors: 1) the effect of wall shear rate on thrombus initiation, 2) the effect of wall shear rate on the growth of thrombi, and 3) the relation between platelet thrombus initiation and intraluminal velocity profile. The range of wall shear rate was up to approximately 1,000 1/sec in venules and from 640 to 2,900 1/sec in arterioles. Platelet thrombus initiation occurred more rapidly at higher wall shear rate in venules and at lower wall shear rate in arterioles. Thrombus initiation time was shortest around a wall shear rate of 900 1/sec in venules and around 700 1/sec in arterioles. Thrombus growth rate in venules was greatest at a wall shear rate of 1,500-2,000 1/sec. Thrombus initiation and its relation to blood flow was also examined in branched and curved microvessels. In these vessels pl...
Relationship between segmental thallium-201 uptake and regional myocardial blood flow in patients with coronary artery disease.
Authors: A BNichols, M BWeiss, R RSciacca, P JCannon, D KBlood
Journal: Circulation (1983)

The relationship between the spatial distribution of thallium-201 in myocardial perfusion scintigrams and the distribution of left ventricular regional myocardial blood flow was examined in 25 patients undergoing coronary arteriography. Thallium-201 myocardial scintigrams were obtained after symptom-limited exercise and after a 4 hr delay. Regional myocardial blood flow was measured by the xenon-133 clearance method in patients at rest and during rapid atrial pacing to a double product comparable with that achieved during exercise stress testing. Patterns of regional thallium-201 activity and regional myocardial blood flow, recorded in similar left anterior oblique projections, were compared for left ventricular segments supplied by the left anterior descending (LAD) and left circumflex (CIRC) arteries. In 11 patients without significant lesions of the left coronary artery (group 1), thallium-201 was homogeneously distributed in the LAD and CIRC distributions in scintigrams taken during peak exercise; the...
The Chromosome Disorders: An Introduction for Clinicians.
Journal: Annals of Internal Medicine (1970)

Several other topics are also discussed such as chromosome damage in somatic cells by environmental agents, linkage analysis by somatic cell hybridization, chromosome abnormalities in the conceptus, and evolution of repetitive DNA's.Considering the theme of the symposium, one is surprised by the lack of discussion of chromosomal polymorphisms (especially ofthe human karyotype) and the role of constitutive heterochromatin in chromosomal evolution.
Presence of negative inotropic agents in canine plasma during positive end-expiratory pressure.
Authors: G AGrindlinger, JManny, RJustice, BDunham, DShepro, H BHechtman
Journal: Circulation Research (1979)

Application of positive end-expiratory pressure (PEEP) will reduce cardiac output (CO). Humoral mediation of this event by circulating negative inotropic agents was examined using a rat papillary muscle bioassay. Twenty-seven dogs were anesthetized with an iv pentobarbital infusion. Plasma was obtained before and after 30 minutes of PEEP. The plasma was oxygenated in a small (4.5-ml) papillary muscle chamber using a diffusion membrane. An average PO2 of 416 mm Hg was achieved. PEEP plasma reduced developed tension (Tpd) from 2.16 +/- 1.0 to 1.90 +/- 1.05 g (P less than 0.0001). A fall in Tpd was observed whether or not CO was maintained constant with fluid infusion. Resting tension was unchanged. The percent reduction in Tpd correlated with the fall in CO (r = 0.63, P less than 0.01) when fluid was not infused to maintain CO. Reapplication of control plasma restored Tpd. Barbiturate levels in anesthetized dogs rose from 17.3 to 19.4 microns/ml during PEEP (P less than 0.1). Addition of pentobarbital to no...
MOLECULAR IMAGING OF TUMOR ASSOCIATED ANGIOGENESIS USING P1227, A NOVEL MRI CONTRAST AGENT TARGETING AVB3 INTEGRIN
Authors: Isabelle Debergh, Nancy Van Damme, Peter Smeets, P Demetter, S Carme, Piet Pattyn, M Peeters, Wim Ceelen
Journal: Annals of Oncology (2009)
Targeting neddylation E2s: a novel therapeutic strategy in cancer
Authors: Yi-Chao Zheng, Yan-Jia Guo, Bo Wang, Chong Wang, M. A. A. Mamun, Ya Gao, Hong-Min Liu
Journal: Journal of Hematology & Oncology (2021)

Abstract Ubiquitin-conjugating enzyme E2 M (UBE2M) and ubiquitin-conjugating enzyme E2 F (UBE2F) are the two NEDD8-conjugating enzymes of the neddylation pathway that take part in posttranslational modification and change the activity of target proteins. The activity of E2 enzymes requires both a 26-residue N-terminal docking peptide and a conserved E2 catalytic core domain, which is the basis for the transfer of neural precursor cell-expressed developmentally downregulated 8 (NEDD8). By recruiting E3 ligases and targeting cullin and non-cullin substrates, UBE2M and UBE2F play diverse biological roles. Currently, there are several inhibitors that target the UBE2M-defective in cullin neddylation protein 1 (DCN1) interaction to treat cancer. As described above, this review provides insights into the mechanism of UBE2M and UBE2F and emphasizes these two E2 enzymes as appealing therapeutic targets for the treatment of cancers.
Clinical Utility Of Duodenal Biopsies In The Diagnosis Of Chronic Diarrhea. A Retrospective Study
Authors: T Voulgaris, M Tampaki, E Laoudi, P Karatzas, G Karamanolis, J Vlachogiannakos, K Papaxoinis, D Kamperoglou, G Papatheodoridis
Journal: Endoscopy (2021)

Aims According to published guidelines, in patients with chronic diarrhea, when no diagnosis can be made by laboratory studies and/or ileocolonoscopy an upper GI endoscopy with duodenal biopsy sampling should be executed. Aim of our study was to access the clinical benefit of such a strategy.
Role of adenosine in pathogenesis of anginal pain.
Authors: FCrea, GPupita, A RGalassi, Hel-Tamimi, J CKaski, GDavies, AMaseri
Journal: Circulation (1990)

The intravenous infusion of adenosine provokes anginalike chest pain. To establish its origin, an intracoronary infusion of increasing adenosine concentrations was given in 22 patients with stable angina pectoris. During adenosine infusion, 20 patients had chest pain without electrocardiographic signs of ischemia. They all reported that the chest pain was similar to their usual anginal pain. In 10 of the 22 patients adenosine was also infused into the right atrium, but it never produced symptoms at the doses that had provoked chest pain during intracoronary infusion. In seven other patients, the intracoronary adenosine infusion was repeated after intravenous administration of aminophylline, an antagonist of adenosine P1-receptors. Aminophylline decreased the severity of adenosine-induced chest pain (assessed with a visual analog scale) from 42 +/- 22 to 23 +/- 17 mm (p less than 0.002). In the remaining five of the 22 patients, monitoring of blood oxygen saturation in the coronary sinus during intracorona...
DBE Insertion Route in Small Bowel Lesions Detected by Capsule Endoscopy: Which Way to go?
Authors: P Cortegoso Valdivia, K Skonieczna-Żydecka, M Pennazio, E Rondonotti, W Marlicz, E Toth, A Koulaouzidis
Journal: Endoscopy (2021)

Aims When capsule endoscopy (CE) examination reveals a small bowel (SB) lesion, selection of the insertion route for double-balloon enteroscopy (DBE) is pivotal. Few progression- and time-based indices/indicators have been proposed for this clinical challenge. In this study, we systematically reviewed the reported success and outcomes of these indicators in determining the DBE route of insertion.
Transcatheter closure of patent foramen ovale after presumed paradoxical embolism.
Authors: N DBridges, WHellenbrand, LLatson, JFiliano, J WNewburger, J ELock
Journal: Circulation (1992)

BACKGROUNDMany have proposed a relation between presence of a patent foramen ovale, with or without atrial septal aneurysm, and cryptogenic stroke. The effect of foramen ovale closure on the risk for subsequent strokes is unknown.METHODS AND RESULTSTranscatheter closure of a patent foramen ovale was undertaken in 36 patients with known right-to-left atrial shunting and presumed paradoxical emboli (31 strokes, 25 transient neurological events, four systemic arterial emboli, and two brain abscesses). Individual patients had between one and four such events. None had a left heart or carotid source of embolism; 31 of 35 had no known risk factors for stroke. Events occurred in 12 patients while they were taking warfarin. At cardiac catheterization, patent foramina ovalia were significantly larger than predicted for age in 67% of the patients. Implantation of a double-umbrella device in the patent foramen ovale was achieved in all without serious procedural complications. Of 34 who have returned for follow-up, ...
Response of nonreentrant catecholamine-mediated ventricular tachycardia to endogenous adenosine and acetylcholine. Evidence for myocardial receptor-mediated effects.
Authors: B BLerman
Journal: Circulation (1993)

BACKGROUNDReentrant ventricular tachycardia (VT) is known to be insensitive to the nucleoside adenosine. However, we have previously identified a form of nonreentrant, catecholamine-mediated VT that can be initiated with rapid pacing, demonstrates cycle length dependence, and is sensitive to exogenous adenosine as well as to the Valsalva maneuver. The mechanism of this tachycardia is thought to be due to a catecholamine-induced, cAMP-mediated increase in intracellular calcium, resulting in delayed afterdepolarizations and triggered activity. The antiarrhythmic effects of exogenous adenosine and Valsalva on this form of VT may be due to receptor-mediated inhibition of adenylate cyclase or to noncardiac receptor-mediated effects, i.e., exogenous adenosine may modulate VT through alterations in autonomic tone by activation of arterial chemoreceptors, and Valsalva has been shown to decrease venous return, resulting in a reduction in cardiac dimensions and myocardial stretch. To clarify this issue and circumve...
Morphology of electrophysiologically identified junctions between Purkinje fibers and ventricular muscle in rabbit and pig hearts.
Authors: JTranum-Jensen, A AWilde, J TVermeulen, M JJanse
Journal: Circulation Research (1991)

Purkinje fiber-ventricular muscle (PV) junctions were identified by extracellular recording in isolated, superfused preparations from rabbit and pig hearts. Microelectrode recordings from different cell types at the PV junctions were obtained, and the cells recorded from were retrieved microscopically. To this end 26 tissue blocks were serially sectioned at 4 microns. Microscopic identification of the very cell recorded from was obtained in five of seven Purkinje, five of 16 transitional, and two of two ventricular muscle cell recordings. In addition, some tissue blocks from both junctional and nonjunctional sites identified only by extracellular recording were examined in serial sections. Transitional cells in the rabbit heart are thin, broad bandlike cells (30-35 by 3-5 microns) arranged in one or two sheets in the subendocardium between the Purkinje layer and ventricular mass. Transitional cells are coupled via short, thin strands to both Purkinje and ventricular muscle cells. A second type of PV coupl...
Angiotensin II increases spontaneous contractile frequency and stimulates calcium current in cultured neonatal rat heart myocytes: insights into the underlying biochemical mechanisms.
Authors: I SAllen, N MCohen, R SDhallan, S TGaa, W JLederer, T BRogers
Journal: Circulation Research (1988)

The effect of angiotensin II on cultured neonatal rat heart myocytes was studied by measuring changes in cell length, the magnitude and kinetics of the calcium current, and changes in cyclic adenosine 3',5'-monophosphate (cAMP) and phosphoinositide metabolism. Spontaneous beating frequency of multicellular networks was increased by angiotensin II with a maximal increase of 100% above control values at concentrations of 5 nM or greater. The half-maximal response occurred at 0.6 nM angiotensin II. Shortening amplitude, shortening velocity, and relaxation velocity decreased concomitantly with the increasing contractile rate. In voltage-clamped single myocytes, both steady-state and transient components of the calcium current were increased by the addition of angiotensin II. Angiotensin II had no effect on either control or isoproterenol-stimulated adenylate cyclase activity in myocyte membranes. Neither the basal levels nor the isoproterenol-stimulated cAMP accumulation in intact cells was affected by additi...
Managed Care: Ethical Issues
Authors: Kathy S. Doner
Journal: JAMA (1995)

To the Editor.  —The conclusion of Drs Emanuel and Dubler,1The physician-patient relationship is the cornerstone for achieving, maintaining, and improving health, is obvious to physicians and patients but largely ignored by the managed health care industry. Essential to an accurate diagnosis is the physician's knowing over time, both cognitively and intuitively, the medical history, the multidimensional aspects of that unique person's life, and the secrets that only a trusting patient reveals. Effective treatment requires an educational approach, a wise presentation of choices, and sometimes a little friendly coercion that again is based on knowledge of the patient over time. It is hoped that some health plans will realize the cost-effective competitive edge that this knowledge provides and will encourage continuity, choice, and adequate patient encounter time.  There is an essential aspect of the physician-patient relationship, however, that was largely ignored by the article—that the relationship itself has therapeutic
Treatment of variant angina with drugs: a survey of 11 cardiology institutes in Japan.
Authors: EKimura, HKishida
Journal: Circulation (1981)

Data from 11 cardiology institutes in Japan were examined to determine the effectiveness of drug therapy, especially with calcium antagonists, on variant angina. The subjects were 243 males and 43 females, most of whom were 40-59 years old. Coronary artery lesions were found in 92 of 162 patients (56.7%) in whom cinecoronary arteriograms were done. The efficacy rates of nifedipine, diltiazem and verapamil were 94.0%, 90.8% and 85.7%, respectively. Regardless of the presence or absence of organic coronary artery lesions, the drugs were effective in 92.3% of the patients with normal or nearly normal coronary arteries and in 82.6% of those with stenosis of more than 50% of the luminal diameter. These findings suggest that the drugs are effective through their antispasmodic actions.