tbuckley/cabot-search huggingface dataset:
Shockwave Lithotripsy Versus Ureteroscopic Treatment as Therapeutic Interventions for Stones of the Ureter (TISU): A Multicentre Randomised Controlled Non-inferiority Trial
Authors: Ranan Dasgupta, Sarah Cameron, Lorna Aucott, Graeme MacLennan, Ruth E. Thomas, Mary M. Kilonzo, Thomas B.L. Lam, James N’Dow, John Norrie, Ken Anson, Neil Burgess, Charles T. Clark, Francis X. Keeley, Sara J. MacLennan, Kath Starr, Sam McClinton
Journal: European Urology (2021)

Renal stone disease is common and can cause emergency presentation with acute pain due to ureteric colic. International guidelines have stated the need for a multicentre randomised controlled trial (RCT) to determine whether a non-invasive outpatient (shockwave lithotripsy [SWL]) or surgical (ureteroscopy [URS]) intervention should be the first-line treatment for those needing active intervention. This has implications for shaping clinical pathways.To report a pragmatic multicentre non-inferiority RCT comparing SWL with URS.This trial tested for non-inferiority of up to two sessions of SWL compared with URS as initial treatment for ureteric stones requiring intervention.The primary outcome was whether further intervention was required to clear the stone, and secondary outcomes included quality of life assessment, severity of pain, and serious complications; these were based on questionnaires at baseline, 8 wk, and 6 mo. We included patients over 16 yr with a single ureteric stone clinically deemed to require intervention. Intention-to-treat and per-protocol analyses were planned.The study recruited between July 1, 2013 and June 30, 2017. We recruited 613 participants from a total of 1291 eligible patients, randomising 306 to SWL and 307 to URS. Sixty-seven patients (22.1%) in the SWL arm needed further treatment compared with 31 patients (10.3%) in the URS arm. The absolute risk difference was 11.7% (95% confidence interval 5.6%, 17.8%) in favour of URS, which was inside the 20% threshold we set for demonstrating noninferiority of SWL.This RCT was designed to test whether SWL is non-inferior to URS and confirmed this; although SWL is an outpatient noninvasive treatment with potential advantages both for patients and for reducing the use of inpatient health care resources, the trial showed a benefit in overall clinical outcomes with URS compared with SWL, reflecting contemporary practice. The Therapeutic Interventions for Stones of the Ureter (TISU) study provides new evidence to help guide the choice of modality for this common health condition.We present the largest trial comparing ureteroscopy versus extracorporeal shockwave lithotripsy for ureteric stones. While ureteroscopy had marginally improved outcome in terms of stone clearance, as expected, shockwave lithotripsy had better results in terms of health care costs. These results should enable patients and health care providers to optimise treatment pathways for this common urological condition.
Abstract 11904: Reduction in Atrial Fibrillation Burden Following Catheter Ablation: Results From the Reveal LINQ Real-world Registry
Authors: Suneet Mittal, Hans-Christoph Diener, Scott E Kasner, Atul Verma, Sean C Beinart, Alpesh N Amin, Erika Pouliot, Noreli C Franco, Andrea Natale
Journal: Circulation (2019)

Background: Unlike external ECG monitoring tools, an insertable cardiac monitor (ICM) has the ability to quantify burden of atrial fibrillation (AF), which has recently been demonstrated to be an i...
Normal left ventricular function.
Authors: J OParker, R BCase
Journal: Circulation (1979)

The Starling relationship in the normal human ventricle may be different than usually portrayed. In normal, resting, supine man the ventricular function curve is at its peak at a left ventricular end-diastolic pressure of approximately 10 mm Hg. Below this point is a strong direct relation between filling pressure and stroke work, while at higher filling pressures, a plateau occurs. Limitation of ventricular response is related to a sharply rising ventricular pressure-volume curve at a normal level of filling pressure. Thus, in the supine position, the normal heart is not on the active portion of the ventricular function curve, but is in a unique position in which cardiac output is probably controlled by factors other than ventricular filling pressure. In ventricular failure, the peak of the ventricular function curve is displaced to a higher level.
Abstract 1009: On the role of DEAR1 as a novel ubiquitin ligase for ER alpha and predictor of tamoxifen response in ER positive breast cancer
Authors: Seetharaman Balasenthil, Nanyue Chen, Ann Killary
Journal: Cancer Research (2019)

Abstract Estrogen receptor positive (ER+) breast cancer accounts for over 70% of breast cancers. Targeted adjuvant therapies aimed at estrogen receptor have changed the natural history of the disease. However, over time many tumors develop resistance mechanisms which result in overall poor outcome. Thus, biomarkers that could predict response to antiestrogens are critically needed and would have major clinical impact. Thus, it is imperative that additional novel mechanisms be discovered not only to understand the basic underlying biology of ER alpha (ERα) signaling in order to identify genetic alterations that deregulate ERα and its role in breast cancer. DEAR1 is a tumor suppressor gene which is mutated, undergoes loss of heterozygosity in breast cancer. Previously we observed a subset of DEAR1 mutations in early onset breast cancers from premenopausal women, therefore we hypothesized that DEAR1 may function in the regulation of ERα signaling and conversely that mutations in DEAR1 (observed in human breast cancers) will abrogate that effect and could play a role in resistance to antiestrogen therapies. To test this hypothesis we studied the effect of DEAR1 expression on ERα. DEAR1 overexpression downregulated ERα expression and stability suggestive that DEAR1 may regulate ER signaling. DEAR1 interacted with ERα by immunoprecipitation and GST pulldown assays. Next we studied whether E3 ligase DEAR1 facilitates the degradation of ERα by promoting the ubiquitination of ERα. Our results indicate that DEAR1 promoted the polyubiquitination of ERα. To assess the effect of DEAR1 on estrogen mediated response, we examined the effect of DEAR1 on ERα-mediated transactivation using ERE-luciferase reporters. Results indicate that DEAR1 significantly inhibits estrogen-mediated transcriptional activity of ERα. We also studied the effect of DEAR1 in antiestrogen resistance using tamoxifen resistant cells. Preliminary results suggest that the presence of DEAR1 promoted the action of antiestrogen in tamoxifen resistant cell line. We have identified a new novel E3 ligase with regulatory effect of ERα signaling and potential implications in antiestrogen resistance. Citation Format: Seetharaman Balasenthil, Nanyue Chen, Ann Killary. On the role of DEAR1 as a novel ubiquitin ligase for ER alpha and predictor of tamoxifen response in ER positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1009.
Deep Neural Network for the Localisation of Early Neoplasia in Barrett’s Oesophagus with Targeted Biopsies
Authors: M Hussein, JG-B Puyal, D Lines, V Sehgal, D Toth, M Everson, G Lipman, O Ahmad, R Kader, JM Esteban, R Bisschops, M Banks, M Haefner, P Mountney, D Stoyanov, L Lovat, R Haidry
Journal: Endoscopy (2021)

Aims To develop a deep neural network to diagnose and localise dysplasia in Barrett’s oesophagus (BE).
Insulin-dependent diabetes mellitus mortality. The risk of cigarette smoking.
Authors: C SMoy, R ELaPorte, J SDorman, T JSonger, T JOrchard, L HKuller, D JBecker, A LDrash
Journal: Circulation (1990)

The relation between cigarette smoking and mortality was examined prospectively in a population of adult insulin-dependent diabetes mellitus (IDDM) patients. In 1981, information on smoking history and other health and lifestyle factors was obtained by questionnaire from 93% of the 723 patients included in the Children's Hospital of Pittsburgh IDDM registry who were diagnosed between 1950 and 1964. Vital status as of January 1, 1988 was ascertained for 98% of the 548 patients who participated in the baseline survey and were alive as of January 1, 1982. Fifty-four cases died during the 6-year follow-up (32 male, 22 female). Proportional hazards analysis revealed that heavy smoking was a significant independent predictor of all-cause mortality among females but not males. The excess mortality in female diabetics was explained primarily by a marked excess risk of coronary heart disease mortality in smokers. These data strongly suggest that cigarette smoking, especially among diabetic females, should be avoid...
Naloxone potentiates cardiopulmonary baroreflex sympathetic control in normal humans.
Authors: H PSchobel, R MOren, A LMark, D WFerguson
Journal: Circulation Research (1992)

Naloxone, an opioid antagonist, augments baroreflex mechanisms in animals; this occurrence suggests that endogenous opioids blunt baroreflex responses. Limited human studies suggest an inhibitory action of endogenous opioids on baroreflex-mediated vagal responses during arterial baroreceptor deactivation. To evaluate the potential effect of endogenous opioids on cardiopulmonary baroreflex mechanisms in humans, we measured arterial and central venous pressures, heart rate, and efferent muscle sympathetic nerve activity (MSNA, by peroneal microneurography) during unloading of cardiopulmonary baroreceptors with incremental lower body negative pressure (LBNP, from 0 to -15 mm Hg) and during the cold pressor test in 21 normal subjects (aged 24 +/- 1 [mean +/- SEM] years). In 14 subjects, we performed LBNP before and after naloxone (0.15 mg/kg i.v.) and placebo (n = 11) on separate days. In six of these 14 subjects and an additional seven subjects (n = 13), studies were also performed before and after administr...
Phasic effects of repetitive vagal stimulation on atrial contraction.
Authors: P JMartin, J RLevy, SWexberg, M NLevy
Journal: Circulation Research (1983)

The vagus nerves of anesthetized dogs were stimulated once each cardiac cycle with a brief burst of pulses, and the timing of the stimulus bursts was changed by a fixed increment on successive cardiac cycles. The effects of such vagal stimulation on atrial contraction depended on the number of pulses per stimulus burst, on the interval between pulses within the burst, and on the timing of the stimulus bursts within the cardiac cycle. The vagal stimulus bursts had the least negative inotropic effect when they were given less than 100 msec before the next atrial depolarization, and they were most effective when given about 330 msec before the next atrial depolarization. This dependence of the inotropic response on the timing of the vagal activity within the cardiac cycle indicates that the following conditions must prevail with respect to the vagal innervation of the atrium: (1) the acetylcholine released from the vagal nerve endings is hydrolyzed at a critically rapid rate in the atrial tissues, (2) the ne...
Quantitative assessment of myocardial ischemia and necrosis by continuous vectorcardiography and measurement of creatine kinase release in patients.
Authors: MSederholm, PGrøttum, LErhardt, JKjekshus
Journal: Circulation (1983)

The accuracy of the use of the maximal QRS vector difference to estimate myocardial infarct size irrespective of infarct location was compared with that of measurement of cumulative creatine kinase (CK) release. Sixty patients with acute myocardial infarction and a history of symptoms of less than 4 hr duration were followed for 24 to 72 hr with orthogonal vectorcardiography and CK release analysis. Spatial QRS vector differences were calculated between the first QRS complex recorded and subsequent QRS complexes at timed intervals. The QRS vector difference increased rapidly and reached a plateau at an average 12.1 hr after onset of symptoms, as compared with 34.0 hr for the cumulated CK release. In 42% of the patients a stepwise progression of infarct evolution was observed. Irrespective of infarct location the maximal spatial ST vector magnitude was related to the ultimate QRS vector difference (r = .80) and to the cumulative amount of CK released (r = .64). Furthermore, maximal QRS vector difference co...
Dynamics of oxygen uptake during exercise in adults with cyanotic congenital heart disease.
Authors: K ESietsema, D MCooper, J KPerloff, M HRosove, J SChild, M MCanobbio, B JWhipp, KWasserman
Journal: Circulation (1986)

The dynamic increase in oxygen uptake (VO2) at the start of exercise reflects the circulatory adjustments to metabolic changes induced by the exercise. Because VO2 measured at the lungs is the product of pulmonary blood flow and arteriovenous oxygen difference, pathologic conditions affecting the capacity of these factors to change would be expected to alter VO2 kinetics. To determine whether measurement of VO2 kinetics can detect conditions in which the pulmonary blood flow response to exercise is abnormal, VO2 was measured, breath-by-breath, during the transition from rest to exercise in 13 adults with cyanotic congenital heart disease (central venoarterial shunting) and in nine normal subjects. The increase in VO2 above baseline during the first 20 sec of exercise (phase I), reflecting the immediate increase in pulmonary blood flow, was diminished in the patients compared with that in normal subjects (14.8 +/- 10.9 vs. 49.8 +/- 19.2 ml of oxygen) (p less than .001). The patients' phase I responses corr...
Medicine and South Africa
Authors: R Stott, I Gordon, P Tinkin, I Leigh, N. Richman, T. Waterston
Journal: BMJ (1986)

SIR,-The president of the Hospital Consultants and Specialists Association states (18 January, p 206) that his association "was very surprised to read the evidenqe of the Short select, committee given by the spokesmen for the medical profession, including the consultant representative on, the BMA delegation, and felt obliged to conduct a survey to.find out if there had been a change of attitude to the hospital staffing structure."As'the "consultant representative" referred to above, I should like to put the-record straight.In 1982 the Central Committee for Hospital Medical Services supported the concept of a controlled.expansion of consultants in general surgery, general medicine, and obstetrics and gynaecology; a reduction in the number of UK graduate registrars in these specilties; and the introduction of an overseas doctors training scheme.These proposals were put to the con- sultant body t large, and 85% of the m,any respondents supported these proposals.This information was included in the select conputtee's *minutes of evidence for Wednesday 27 March 1985, to which the president of the HCSA referred in his letter.Indeed, it states quite clearly i'n those minutes (p 6, paragraph 16) that " HC:MS did not support the Social Servies Committee's geieral notion of a consultant provided service."-In oral evidence used the-phrase "consultant based," and from the subsequent paragraphs itis clear that I was using the phrase.todescribe the proposals tharhad been accepted by the profession in 1982.This includes an adequate numnber of
Effects of the KATP channel opener bimakalim on coronary blood flow, monophasic action potential duration, and infarct size in dogs.
Authors: ZYao, G JGross
Journal: Circulation (1994)

BACKGROUNDThe major purpose of the present study was to determine the effect of the potassium channel opener bimakalim, administered intracoronary only during the initial 10 minutes of ischemia, on myocardial infarct size in anesthetized dogs. A second aim was to test the possibility that bimakalim mediates its cardioprotective effects by accelerating the rate of myocyte action potential shortening during early ischemia. A third aim was to determine the relative potency of bimakalim to open coronary vascular ATP-regulated potassium (KATP) channels versus myocyte KATP channels.METHODS AND RESULTSBarbital-anesthetized open-chest dogs were used. In the initial studies, bimakalim (0.1 to 10 micrograms/min) was infused into the left anterior descending coronary artery (LAD), and changes in coronary blood flow and monophasic action potential duration (MAPD) were used as indexes of coronary vascular KATP channel and myocyte KATP channel activity, respectively. In subsequent infarct studies, dogs were subjected t...
Nine in 10 professional organisations say doctors should have to register their financial interests
Authors: Abi Rimmer
Journal: BMJ (2021)

Nearly 90% of organisations representing doctors agree that the UK should have a mandatory and public register of doctors’ interests, a survey by The BMJ has found.

Last year the Independent Medicines and Medical Devices Safety Review, chaired by Julia Cumberlege, called for the General Medical Council (GMC) to expand its register to include a list of financial and non-pecuniary interests for all doctors.1

That review investigated harmful side effects caused by the hormone pregnancy test Primodos, the anti-epileptic drug sodium valproate, and surgical mesh. One of its key conclusions was that patients had a right to know if their doctor had financial or other links with pharmaceutical or medical device companies.

The BMJ wrote to six faculties, 14 royal medical colleges, and the Academy of Medical Royal Colleges about such a register. It received responses from two faculties, 12 colleges, and the academy, a 71% response rate.

Of the organisations that responded, 13 (87%) agreed that there should be a mandatory and public register of doctors’ interests in the UK. The Faculty of Intensive Care Medicine also agreed with the proposal but only if substantial investments were declared and the cost …
Physiological concentrations of nitric oxide do not elicit an acute negative inotropic effect in unstimulated cardiac muscle.
Authors: A SWeyrich, X LMa, MBuerke, TMurohara, V EArmstead, A MLefer, J MNicolas, A PThomas, D JLefer, JVinten-Johansen
Journal: Circulation Research (1994)

We examined the effect of several nitric oxide (NO) donors, authentic NO gas, and L-arginine in isolated cat and rat papillary muscles. We did not observe significant inotropic effects in response to any NO donor (ie, SPM-5185, C87-3754, and S-nitroso-N-acetylpenicillamine [SNAP]) from 1 nmol/L to 100 mumol/L. Similarly, authentic NO, at concentrations far in excess of those that maximally dilate the coronary vasculature (ie, 500 nmol/L), also failed to exert a detectable inotropic effect in these preparations. However, in the presence of 5 mumol/L norepinephrine, 500 nmol/L NO exerted a 12 +/- 3% decrease in isolated rat papillary muscle contractility (P < .05). Addition of L-arginine up to 25 mmol/L exerted no inotropic effects in isolated rat papillary muscles. However, at 50 mmol/L, L-arginine decreased contractile force by 21 +/- 4% (P < .01). On further examination, the negative inotropic effect of 50 mmol/L L-arginine appeared to be nonspecific, since the inactive stereoisomer, D-arginine, at 50 mm...
Ultrasonic plaque ablation. A new method for recanalization of partially or totally occluded arteries.
Authors: R JSiegel, M CFishbein, JForrester, KMoore, EDeCastro, LDaykhovsky, T ADonMichael
Journal: Circulation (1988)

The potential application of ultrasonic energy for ablation of atherosclerotic plaques was studied in human atherosclerotic arteries with continuous and pulsed delivery of energy. With a prototype ultrasonic wire probe (n = 79 segments), there was gross reduction in vascular lesions as well as microscopic disruption of fibrous and calcified plaques. Normal portions of vessels appeared unaffected by the application of ultrasound. The prototype ultrasonic wire catheter ablated calcific deposits in less than 10 seconds. With this probe, all 26 complete atherosclerotic occlusions 0.5-5 cm in length were recanalized irrespective of the presence of calcium. Twenty-four of the segments were reopened in less than 20 seconds. By light microscopy, the site of plaque ablation was smooth, concave, and conformed to the shape of the probe tip. In 17 samples, there was evidence of thermal injury, and in six of the 79 samples studied with the prototype probe, there was vascular perforation. No vascular perforation occurr...
Immediate intraportal transplantation of human bone marrow mesenchymal stem cells prevents death from fulminant hepatic failure in pigs
Authors: Tao Wei, Yi Lv
Journal: Hepatology (2012)

We read with much interest the article by Li et al.1 This elegant study indicated that intraportal transplantation of human bone marrow mesenchymal stem cells (hBMSCs) could achieve better liver function recovery and long-term survival in pigs with fulminant hepatic failure (FHF), whereas animals either in the sham group or receiving hBMSCs through the peripheral vein died within 4 days after D-galactosamine injection. We believe that the transplantation procedure was performed immediately after the induction of liver failure according to the title, though interval time between the two interventions was not mentioned clearly in the Materials and Methods section. Because the immediate treatment might not be available for patients with FHF in the clinical setting, whether delayed treatment remains beneficial would be more significant, as proposed by other researchers.2 Given that pigs without cell transplantation could still survive for a mean of 2.9 days, we wonder whether the investigators examined the influence of different lengths of intervals on outcomes. The investigators also explored the mechanisms underlying the efficacy of intraportal hBMSC administration for FHF. It is encouraging to know that approximately 30% of hepatocytes are derived from hBMSCs 2-10 weeks after transplantation. On the other hand, BMSCs possess the ability to transdifferentiate into myofibroblasts that produce extracellular matrix (ECM) constituent and contribute to tissue repair.3 One recent study demonstrated that acute liver failure triggered the activation of hepatic stellate cells and enhanced the formation of ECM, which reciprocally provide an optimal architecture for support of hepatocyte repopulation.4 Among animals assigned to the intraportal transplantation group, an approximately and completely healthy liver structure was exhibited at weeks 3 and 5, respectively. It is likely that hBMSC-derived parenchymal and nonparenchymal cells coevolve in facilitating the regenerative process. Do the investigators have histological data about transdifferentiation of hBMSCs into myofibroblasts, which would be of interest for further elucidation of mechanisms? Tao Wei M.D.* , Yi Lv M.D., Ph.D.* , * Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China, Institute of Advanced Surgical Technology and Engineering, Xi'an Jiaotong University, Xi'an, China.