tbuckley/cabot-search huggingface dataset:
Mouse model of arterial injury.
Authors: VLindner, JFingerle, M AReidy
Journal: Circulation Research (1993)

In the present study, we established an injury model of the mouse carotid artery. Complete removal of the endothelium was achieved with a flexible wire. A platelet monolayer covered the denuded surface, and damage to underlying medial smooth muscle cells (SMCs) was detected. Injection of [3H]thymidine was used to determine the replication index for medial SMCs, which was found to be 1.6% at 2 days after denudation and 9.8% at 5 days. SMCs were observed in the intima by day 8 (replication index, 66%), and by 2 weeks the intimal lesion had a similar cell content as the media. In most animals, repair of the endothelial lining was complete 3 weeks after injury. The present model will allow us to use transgenic animals to address questions relevant to vascular biology and atherosclerosis.
Hybrid Endoscopic Mucosal Resection Combining Conventional Mucosectomy and Full-Thickness Resection Using the FTRD System: Two Practical Applications of Difficult Colorectal Lesions
Authors: C Macedo, E Gravito-Soares, M Gravito-Soares, C Correia, J Estorninho, P Amaro, P Narra Figueiredo
Journal: Endoscopy (2021)

Case 1 An 80-year-old man with multiple comorbidities underwent colonoscopy identifying a 30mm mixed granular-nodular LST in a region of multiple diverticula in sigmoid colon. Almost complete fragmented mucosectomy was performed, except a small pericentimetric area that involved a diverticular orifice. Case 2 A 68-year-old man, diabetic, obese with liver transplantation underwent colonoscopy identifying a 40mm mixed granular-nodular LST in hepatic flexure that was submitted to incomplete fragmented mucosectomy due central area without elevation. Both residual lesions were resected combining full-thickness resection using the FTRD system without complications. This successful minimally invasive technique allows avoiding surgical morbidity in high-risk patients.
Letter to the editor
Authors: Sinasi Ozsoylu
Journal: American Journal of Hematology (1984)

Although the relationship between the administration of iocetamic acid and the occurrence of thrombocytopenia appears convincing, I believe that antiplatelet antibodies should be sought in the serum of the patient to exclude the occurrence of concomitant idiopathic immune thrombocytopenia (ITP).Since antiplatelet antibodies persist in ITP [ 1,2], serial examination of the patient's serum might help differentiate between druginduced thrombocytopenia and ITP.If antiplatelet antibodies were not demonstrated in the patient's serum, in vitro studies in which the serum from a patient who had ioacetic acid for a cholecytographic examination might be utilized in the antiplatelet antibody test to help in separating whether a drug-induced or idiosyncratic reaction had occurred.
Models of the Physician-Patient Relationship
Authors: Judith Andre
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Emanue<sup>1</sup>and Emanuel<sup>1</sup>argue for a "deliberative" model of the physician-patient relationship. The model conceives of patient autonomy as the capacity for moral self-development in matters of health. It holds that the "aim of the physician-patient interaction is to help the patient determine and choose the best health-related values." How? By presenting information, by helping the patient clarify the values at stake, and then by articulating what should be done and persuading the patient. "Deliberation" is an attractive way to think of the physicianpatient conversation. It suggests rationality and responsibility; it suggests that the two parties, together, think something through. The details of their model, however, do not fit comfortably with their formal ideal. Moral reasoning, like any kind of thinking, is fostered in a variety of ways. Telling someone the answer and how to reach it is not the most important of these, except when
Development and maintenance of renal hypertension in normal and guanethidine sympathectomized rats.
Authors: J RDouglas, E MJohnson, G RMarshall, JHeist, B KHartman, PNeedleman
Journal: Circulation Research (1975)

The sympathetic nervous system has been postulated to play a role in the maintenance of renal hypertension. Permanent peripheral sympathectomy was performed by treating newborn rats for 21 days with guanethidine. Sympathectomy was confirmed by (1) relative insensitivity to tyramine, (2) lack of responsiveness to renal nerve stimulation, and (3) absence of dopamine-beta-hydroxylase immunofluorescence in renal blood vessels. Placement of a clip on the left renal artery led to the development of two-kidney renal hypertension. No differences were observed between the two-kidney renal hypertensive normal and sympathectomized rats; both had elevated plasma renin activity and vasodepression with angiotensin antagonists which were maintained up to nine weeks. Furthermore, in normal rats chronic beta-adrenergic blockade with propranolol caused no change in the development of the two-kidney renal hypertension. Similarly, no differences were seen in blood pressure, plasma renin activity, or response to antagonists b...
Transient predominant right ventricular ischemia caused by coronary vasospasm.
Authors: OParodi, PMarzullo, DNeglia, MGalli, ADistante, DRovai, AL'Abbate
Journal: Circulation (1984)

This study describes the clinical experience with four patients with variant angina caused by spasm of the right coronary artery who were assessed for evidence of right ventricular involvement. The patients were suspected of having predominant right ventricular ischemia on the basis of normal thallium-201 scans, left ventricular ejection fraction, regional wall motion assessed by equilibrium radionuclide angiography (RNA), two-dimensional echocardiographic findings, and left ventricular hemodynamics; all procedures were performed during transient ST segment elevation in the inferior leads. Right ventricular ischemia was documented in four patients by first-pass radionuclide studies and phase analysis of RNA, and in three patients by simultaneous right and left hemodynamic monitoring. The clinical findings from these four patients are compared with those from four other patients with similar electrocardiographic changes, coronary anatomic distribution, and documented right coronary spasm but with evidence ...
Complement C3a and C5a receptor blockade modulates regulatory T cell conversion in head and neck cancer
Authors: Jacob Gadwa, Thomas E Bickett, Laurel B Darragh, Michael William Knitz, Shilpa Bhatia, Miles Piper, Benjamin Van Court, Shiv Bhuvane, Diemmy Nguyen, Varuna Nangia, Emily K Kleczko, Raphael A Nemenoff, Sana D Karam
Journal: Journal for ImmunoTherapy of Cancer (2021)

Resistance to therapy is a major problem in treating head and neck squamous cell carcinomas (HNSCC). Complement system inhibition has been shown to reduce tumor growth, metastasis, and therapeutic resistance in other tumor models, but has yet to be explored in the context of HNSCC. Here, we tested the effects of complement inhibition and its therapeutic potential in HNSCC. We conducted our studies using two Human Papilloma Virus (HPV)-negative HNSCC orthotopic mouse models. Complement C3aR and C5aR1 receptor antagonists were paired with radiation therapy (RT). Tumor growth was measured and immune populations from tumor, lymph node, and peripheral blood were compared among various treatment groups. Genetically engineered mouse models DEREG and C3-/- were used in addition to standard wild type models. Flow cytometry, clinical gene sets, and in vitro assays were used to evaluate the role complement receptor blockade has on the immunological makeup of the tumor microenvironment. In contrast to established literature, inhibition of complement C3a and C5a signaling using receptor antagonists accelerated tumor growth in multiple HNSCC cell lines and corresponded with increased frequency of regulatory T cell (Treg) populations. Local C3a and C5a signaling has importance for CD4 T cell homeostasis and eventual development into effector phenotypes. Interruption of this signaling axis drives a phenotypic conversion of CD4+ T cells into Tregs, characterized by enhanced expression of Foxp3. Depletion of Tregs reversed tumor growth, and combination of Treg depletion and C3a and C5a receptor inhibition decreased tumor growth below that of the control groups. Complete knockout of C3 does not harbor the expected effect on tumor growth, indicating a still undetermined compensatory mechanism. Dexamethasone is frequently prescribed to patients undergoing RT and inhibits complement activation. We report no deleterious effects associated with dexamethasone due to complement inhibition. Our data establish Tregs as a pro-tumorigenic driver during complement inhibition and provide evidence that targeted C3a and C5a receptor inhibition may add therapeutic advantage when coupled with anti-Treg therapy.
Non-Curative Endoscopic Submucosal Dissection (ESD) for Colorectal Cancer: Clinical Outcomes and Predictors of Recurrence
Authors: M Spadaccini, M Bourke, R Maselli, M Pioche, P Bhandari, J Jacques, A Haji, D Yang, E Albeniz, M Kaminski, H Messmann, A Herreros de Tejada, S Sferrazza, B Pekarek, J Rivory, S Geyl, S Gulati, P Draganov, N Shahidi, H Ejaz, C Fleishmann, E Vespa, A Iannone, A Alkandari, C Hassan, A Repici
Journal: Endoscopy (2021)

Aims Endoscopic submucosal dissection(ESD)is an organ-preserving approach pursuing curative intent for the removal of superficially invasive colorectal cancers(CRCs) with negligible risk for lymph-node metastasis. Conversely, additional surgical resection is recommended in case of high risk of nodal involvement based on histo-pathological features. However, both the actual risk of a lymph-node disease and the clinical outcomes of patients who underwent non-curative ESD has never been investigated. The aim of this study is to report outcomes of these patients from a large Western cohort.
An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence.
Authors: IHolme
Journal: Circulation (1990)

The primary aim of this study was to estimate the relation between cholesterol reduction and total mortality and coronary heart disease (CHD) incidence. Secondarily, the clinical issues of whether the efficacy of cholesterol lowering is dependent on the treatment modality, presence of CHD at baseline, or the simultaneous introduction of other interventions was explored. All randomized clinical intervention trials of cholesterol reduction were used in an overview analysis of total mortality rate and CHD incidence; analysis was performed with weighted linear regression. The trials include those that used primary and secondary intervention, diet and drugs, and single or multifactor design. Nineteen trials were analyzed for total mortality, and of the 19, 16 were analyzed for CHD incidence rate. Net difference in cholesterol change between study groups was used as the independent variable, and the three previously mentioned dichotomous design characteristics were used as additional independent variables. For ...
The electrocardiographic and antiarrhythmic effects of imipramine hydrochloride at therapeutic plasma concentrations.
Authors: E GGiardina, J TBigger, A HGlassman, J MPerel, S JKantor
Journal: Circulation (1979)

The electrocardiographic effects of imipramine hydrochloride at therapeutic plasma concentrations were determined in 44 depressed patients during a 6-week clinical outcome study of depression. During each week of the protocol, i.e., 2 weeks of control and 4 weeks of drug treatment, a standard 12-lead ECG, high-speed, high-fidelity ECG tracings, and a 24-hour continuous ECG recording were obtained. PR, QRS, and QTc intervals, T-wave amplitude, heart rate and frequency of ventricular premature depolarizations (VPDs) were measured. The plasma concentration of imipramine and desmethylimipramine was measured three times a week. Imipramine prolonged the PR (p less than 0.001), QRS (p less than 0.001) and QTc (p less than 0.001) intervals, increased the heart rate (p less than 0.001) and lowered T-wave amplitude (p less than 0.05) during the 4 weeks of treatment. No patient developed high-grade atrioventricular block or severe intraventricular conduction abnormalities. In addition, imipramine had a potent antiar...
Cellular electrophysiological changes during ischemia in isolated, coronary-perfused cat ventricle with healed myocardial infarction.
Authors: SKimura, A LBassett, J SCameron, HHuikuri, P LKozlovskis, R JMyerburg
Journal: Circulation (1988)

Cellular electrophysiological consequences of acute ischemia superimposed on healed myocardial infarction were studied in isolated, coronary-perfused cat left ventricles 2-4 months after ligation of multiple distal tributaries of the left anterior descending and circumflex coronary arteries. Oxygenated Tyrode's solution was perfused through the left anterior descending and circumflex coronary arteries, and the preparations were superfused with Tyrode's solution gassed with 95% N2-5% CO2. Transmembrane action potentials were recorded from the endocardial cells in normal and infarcted zones. There were no significant differences in measured action potential variables and refractory periods between cells in the normal and infarcted zones before acute ischemia. When coronary perfusion was discontinued (ischemia), resting potential, action potential amplitude, and action potential duration were reduced, and the refractory period was shortened progressively in cells of the normal zone. However, the action pot...
Treatment of oesophageal ulcerations using endoscopic transplantation of tissue-engineered autologous oral mucosal epithelial cell sheets in a canine model
Authors: G. P Yang, R. M Soetikno
Journal: Gut (2007)

Endoscopic transplantation in oesophageal ulceration

The late transplantation pioneer, Norman Shumway, MD, was fond of saying, “The future of transplantation is xenotransplantation. And, it always will be.” Tissue engineering, the in vitro creation of functional replacement tissues, has been proposed as a way to replace lost or damaged tissues due to acute or chronic disease for nearly 20 years.1 Despite the tremendous interest, there are a few tissue-engineered constructs that have gained considerable acceptance in clinical use, although progress is being made. Ohki et al 2, demonstrate recent progress of the potential application of tissue engineering in endoscopy.

The complexity of organs and the lack of knowledge of how these organs are patterned in their development have made tissue engineering of solid organs like the liver difficult.3 In the case of the liver, the construct must have two separate vascular inflows, a single vascular outflow and a separate biliary drainage system. This also necessitates a particular polarity in the organisation of hepatocytes. Thus, despite the desire and need to replace liver allografts as a treatment for end-stage liver disease, there is no solution in sight. Because of the complexity of many solid organs, tissue engineering has turned to relatively simpler structures like bone, cartilage and skin, and it is likely that the first clinically successful tissue engineered construct will be one of these tissues.

In the study by Ohki et al 2, the authors are not engineering an entire oesophagus, but rather are attempting a simpler task. Their goal is the restoration of the protective stratified epithelium after endoscopic submucosal dissection using cultured sheets of cells harvested from the buccal mucosa. They report short-term survival of these grafts with improved healing or the areas of …
Kinetics of C5a release in cardiac lymph of dogs experiencing coronary artery ischemia-reperfusion injury.
Authors: W JDreyer, L HMichael, TNguyen, C WSmith, D CAnderson, M LEntman, R DRossen
Journal: Circulation Research (1992)

Previous studies of myocardial ischemia suggest that complement activation may play a central role in the inflammatory response during reperfusion. Our previous work has demonstrated neutrophil chemotactic activity to be present in reperfusion canine cardiac lymph after myocardial ischemia and infarction. To evaluate the contribution of the complement-dependent anaphylatoxin C5a to this neutrophil chemotactic activity, rabbit antiserum to canine C5a was prepared. At dilutions > 1:500 but < 1:2,000, the antiserum abolished the ability of zymosan-activated dog serum to induce a ruffled, bipolar morphology in isolated neutrophils used as a bioassay of chemotactic stimulation. This antiserum did not affect similar morphological changes in neutrophils exposed to platelet activating factor (10(-7)-10(-6) M) or recombinant human interleukin-8 (10(-9)-10(-8) M); thus, we deemed it functionally specific for canine C5a. In a pattern similar to what we previously reported, cardiac lymph collected before a 1-hour lig...
Coronary artery vasoconstriction routinely occurs after percutaneous transluminal coronary angioplasty. A quantitative arteriographic analysis.
Authors: T AFischell, GDerby, T MTse, M LStadius
Journal: Circulation (1988)

To determine whether percutaneous transluminal coronary angioplasty (PTCA) increases coronary artery luminal dimensions by stretching and injuring (paralyzing) the smooth muscle of the arterial wall, we prospectively analyzed spontaneous changes and then intracoronary nitroglycerin-induced changes in segmental coronary artery diameters during the first 30 minutes after uncomplicated single-vessel PTCA in 10 patients. Five additional patients received intravenous nitroglycerin throughout the procedure to determine whether nitroglycerin could prevent vasoconstriction after PTCA. All of the patients were maintained on oral doses of diltiazem and aspirin at the time of the study. Coronary arteriography was performed at 2, 5, 15, and 30 minutes after PTCA and then 3 minutes after 300 micrograms i.c. nitroglycerin. Quantitative measurements (computerized edge-detection) were performed at each time, in coronary segments centered in the dilated segment, distal to the dilated segment, and in a control vessel not...
Endoscopic Papillary Large Balloon Dilatation Without Preceding Sphincterotomy For Removal Choledocholithiasis In Patients With ROUX-EN-Y Surgery
Authors: J Espinel, E Pinedo
Journal: Endoscopy (2021)

Aims We retrospectively evaluated the feasibility and safety of endoscopic papillary large balloon dilatation without preceding sphincterotomy for the removal of choledocholithiasis.
Transdermal modification of platelet function. A dermal aspirin preparation selectively inhibits platelet cyclooxygenase and preserves prostacyclin biosynthesis.
Authors: R MKeimowitz, GPulvermacher, GMayo, D JFitzgerald
Journal: Circulation (1993)

BACKGROUNDEven low doses of oral aspirin inhibit prostacyclin (prostaglandin [PG] I2) formation and cause gastrointestinal toxicity. We examined the skin as a novel route for continuous low-dose aspirin administration and selective inhibition of platelet cyclooxygenase in humans.METHODS AND RESULTSAspirin 250 or 750 mg/d for 10 days induced a dose-dependent inhibition of serum thromboxane (TX) B2. At the highest dose, five of six subjects responded, with a mean reduction in serum TXB2 of 95 +/- 3% (P = .003). Urinary 2,3-dinor TXB2, an index of in vivo TXA2 formation, decreased by 68 +/- 7% and recovered slowly, consistent with inhibition of platelet cyclooxygenase in vivo. In contrast, PGI2 biosynthesis, determined as excretion of 2,3-dinor-6-keto PGF1 alpha, was 81 +/- 5% of baseline at 10 days. Intravenous bradykinin increased PGI2 biosynthesis 5.1 +/- 1.6-fold (n = 4) before aspirin treatment. Oral aspirin 75 mg/d for 14 days abolished bradykinin-induced PGI2 formation, whereas dermal aspirin 750 mg/d...
Determination of the Optimal Electrical Field Strength for Inducing Apoptosis in the Rat Stomach During Irreversible Electroporation&amp;NBSP
Authors: HJ Jeon, HJ Chun, B Keum, YT Jeen, ES Kim, HS Choi, JM Lee, KW Lee, SH Kim, EJ Bang, JW Seo, YW Ha, HS Lee
Journal: Endoscopy (2021)

Aims Irreversible electroporation (IRE) is a tissue ablation technique inducing apoptosis. However, the most efficient electrical field strength for IRE has not been determined. We aimed to investigate the optimal electrical field strength for IRE to promote gastric tissue apoptosis and identify post-IRE tissue recovery.
Altered skeletal muscle metabolic response to exercise in chronic heart failure. Relation to skeletal muscle aerobic enzyme activity.
Authors: M JSullivan, H JGreen, F RCobb
Journal: Circulation (1991)

BACKGROUNDExertional fatigue, which frequently limits exercise in patients with chronic heart failure, is associated with early anaerobic metabolism in skeletal muscle. The present study was designed to examine the skeletal muscle metabolic response to exercise in this disorder and determine the relation of reduced muscle blood flow and skeletal muscle biochemistry and histology to the early onset of anaerobic metabolism in patients.METHODS AND RESULTSWe evaluated leg blood flow, blood lactate, and skeletal muscle metabolic responses (by vastus lateralis biopsies) during upright bicycle exercise in 11 patients with chronic heart failure (ejection fraction 21 +/- 8%) and nine normal subjects. In patients compared to normal subjects, peak exercise oxygen consumption was decreased (13.0 +/- 3.3 ml/kg/min versus 30.2 +/- 8.6 ml/kg/min, p less than 0.01), whereas peak respiratory exchange ratio and femoral venous oxygen content were not different (both p greater than 0.25), indicating comparable exercise end p...
Impact of COVID-19 lockdown on emergency asthma admissions and deaths: national interrupted time series analyses for Scotland and Wales
Authors: Gwyneth A Davies, Mohammad A Alsallakh, Shanya Sivakumaran, Eleftheria Vasileiou, Ronan A Lyons, Chris Robertson, Aziz Sheikh
Journal: Thorax (2021)

The COVID-19 pandemic's impact on people with asthma is poorly understood. We hypothesised that lockdown restrictions were associated with reductions in severe asthma exacerbations requiring emergency asthma admissions and/or leading to death.Using data from Public Health Scotland and the Secure Anonymised Information Linkage Databank in Wales, we compared weekly counts of emergency admissions and deaths due to asthma over the first 18 weeks in 2020 with the national averages over 2015-2019. We modelled the impact of instigating lockdown on these outcomes using interrupted time-series analysis. Using fixed-effect meta-analysis, we derived pooled estimates of the overall changes in trends across the two nations. We also investigated trends in asthma-related primary care prescribing and emergency department (ED) attendances in Wales.Lockdown was associated with a 36% pooled reduction in emergency admissions for asthma (incidence rate ratio, IRR: 0.64, 95% CI: 0.49 to 0.83, p value 0.001) across both countries. There was no significant change in asthma deaths (pooled IRR: 0.57, 95% CI: 0.17 to 1.94, p value 0.37). ED asthma attendances in Wales declined during lockdown (IRR: 0.85, 95% CI: 0.73 to 0.99, p value 0.03). A large spike of 121% more inhaled corticosteroids and 133% more oral corticosteroid prescriptions was seen in Wales in the week before lockdown.National lockdowns were associated with substantial reductions in severe asthma exacerbations leading to hospital admission across both Scotland and Wales, with no corresponding increase in asthma deaths.