tbuckley/cabot-search huggingface dataset:
Acute and chronic dose-response relationships for angiotensin, aldosterone, and arterial pressure at varying levels of sodium intake.
Authors: A WCowley, R EMcCaa
Journal: Circulation Research (1976)

We examined the acute and chronic dose-response relationships between intravenously infused angiotensin II (A II) and the resulting changes in arterial pressure and plasma aldosterone concentration at varying levels of sodium intake. Sequential analysis of plasma aldosterone at each A II infusion rate resulted in an acute dose-related increase in plasma aldosterone which was markedly attenuated after the first 24 hours of infusion, the final level being directly related to the dose of A II and inversely related to sodium intake. A II infused at 5,15, and 23 ng/kg per min was associated with an initial increase (2nd to 8th hour) in plasma aldosterone to 2,6, and 9 times control values, respectively, in dogs receiving 40 mEq Na+/day. But, after the 1st day, aldosterone averaged only 1, 1.7, and 3 times control values for the next 2 weeks at the same rates of A II infusion. Dogs receiving 120 mEq Na+/day during A II infusion exhibited only a transient increase in plasma aldosterone during the 1st day. Sustai...
Clinical validity of a negative venogram in patients with clinically suspected venous thrombosis.
Authors: RHull, JHirsh, D LSackett, D WTaylor, CCarter, A GTurpie, PPowers, MGent
Journal: Circulation (1981)

Although it is generally accepted that negative venography excludes deep vein thrombosis (DVT) in patients in whom it is clinically suspected, there is no evidence to support this conclusion. To test the correctness of withholding anticoagulant therapy in these patients, we followed 160 consecutive patients who had clinically suspected DVT and negative venograms to determine the frequency of postvenographic DVT. Anticoagulant therapy was withheld in all patients. No patient died or developed pulmonary embolism during 3 months of follow-up. Two of the 160 patients (1.3%) attended the clinic on an emergency basis during follow-up with new symptoms of DVT and in both patients, DVT was confirmed by objective testing. These events developed within 5 days of venography, which suggests that they were induced by venography. Nevertheless, the findings indicate it is safe to withhold treatment in patients with clinically suspected DVT and negative venograms.
Noninvasive assessment of mitral insufficiency by transcutaneous Doppler ultrasound.
Authors: P MNichol, D RBoughner, J APersaud
Journal: Circulation (1976)

Instantaneous aortic arch blood velocity was recorded transcutaneously from the suprasternal notch, using a 2.2 MHz Doppler ultrasound unit, in 18 normals and 16 patients undergoing cardiac catheterization who had murmurs of mitral regurgitation. In normals aortic blood velocity rose rapidly in early systole to a midsystolic peak then fell to zero velocity. These roughly parabolic patterns had area ratios beneath the first and second halves of the curves measuring 52:48 +/- 3 (SD). With increasingly severe mitral regurgitation the pattern became skewed leftward such that the percent in the first half of systole ranged from 53-79%. From the angiograms of our sixteen patients an estimate of true percent regurgitation was made using the Fick cardiac output and ventricular volume measurements. When compared with the area under the first half of the velocity curve a strong correlation was found (r = 0.84) indicating that this Doppler technique can be used to evaluate mitral insufficiency.
Tunnel subaortic stenosis: left ventricular outflow tract obstruction produced by fibromuscular tubular narrowing.
Authors: B JMaron, D RRedwood, W CRoberts, W LHenry, A GMorrow, S EEpstein
Journal: Circulation (1976)

The clinical and morphologic features of tunnel subaortic stenosis, an unusual form of obstruction to left ventricular outflow, are described in 11 patients. Although patients with tunnel subaortic stenosis demonstrate a variety of cardiovascular malformations, the most characteristic anatomic feature is fibromuscular tubular narrowing of the outflow tract that remains relatively unchanged during the cardiac cycle. The aortic anulus was abnormally small in six of the 11 patients, including one who also had a hypoplastic ascending aorta. Evidence of a small mitral orifice was present in two patients, and two other patients had asymmetric septal hypertrophy. Although operation was successful in significantly reducing the outflow gradient in two of the seven operated patients, all seven patients had gradients of 50 mm Hg or more at the most recent postoperative evaluation. Three patients (two with previous operation) died suddenly; each of these patients had mild or no symptoms. Because of the apparent ineff...
Predictive value of the exercise tolerance test for mortality in North American men: the Lipid Research Clinics Mortality Follow-up Study.
Authors: D JGordon, L GEkelund, J MKaron, J LProbstfield, CRubenstein, L TSheffield, LWeissfeld
Journal: Circulation (1986)

More than 3600 white men, from 30 to 79 years old and without a history of myocardial infarction, underwent submaximal treadmill exercise tolerance tests as part of their baseline evaluation for the Lipid Research Clinics Mortality Follow-up Study. The exercise test was conducted according to a common protocol and coded centrally; depression of the ST segment by at least 1 mm (visual coding) and/or 10 microV-sec (ST integral, computer coding) signified a positive test. Concurrent measurements of age, blood pressure, history of cigarette smoking, and plasma levels of lipids, lipoproteins, and glucose, as well as other coronary risk factors, were obtained. Cumulative mortality from cardiovascular disease was 11.9% (22/185) over 8.1 years mean follow-up among men with a positive exercise test vs 1.2% (36/2993) over 8.6 years mean follow-up among men with a negative test. Three-quarters (43) of these deaths were due to coronary heart disease. The relative risk for cardiovascular mortality associated with a po...
Adenine nucleotide metabolism and compartmentalization in isolated adult rat heart cells.
Authors: TGeisbuhler, R AAltschuld, R WTrewyn, A ZAnsel, KLamka, G PBrierley
Journal: Circulation Research (1984)

The metabolism and intracellular compartmentalization of adenine nucleotides in a preparation of adult rat heart myocytes showing good morphology, viability, and tolerance to calcium ion has been examined by high performance liquid chromatography. These myocytes contain an average of 23 nmol adenine nucleotide per milligram protein which is about 60% of the adenine nucleotide content of intact rat heart tissue. The loss of adenine nucleotide occurs during the incubation and washing steps that increase the yield of viable cells, rather than during the collagenase perfusion. An analysis of cellular compartments shows that the adenine nucleotide of the cell consists of 17 nmol adenine nucleotide in the cytosol, 5 nmol in the mitochondria, and 1.3 nmol adenosine diphosphate bound to myofibrils per milligram cell protein. Myocytes lose both adenosine triphosphate and adenine nucleotide when incubated anaerobically in the absence of glucose, and the lost adenine nucleotide can be accounted for as increased inos...
Modification of sinus node function by epicardial laser irradiation in dogs.
Authors: LLittmann, R HSvenson, J JGallagher, SBharati, MLev, K DLinder, G PTatsis, CNichelson
Journal: Circulation (1990)

This study tested the feasibility of neodymium:YAG laser photocoagulation of selected sinus node areas to depress sinus rate responsiveness. In 14 open-chest dogs, origin of the sinus impulse (O point) was electrically mapped from the epicardium before and during isoproterenol infusion. Epicardial laser photocoagulation was applied to the O point observed during isoproterenol infusion and stepwise to remapped new O points until a 30 +/- 5% decrease in heart rate occurred. Long-term effects were assessed by Holter monitoring and electropharmacologic testing preoperatively and up to 10 weeks or 6 months. Mean (+/- SEM) percent decreases were observed at 10 weeks in the following parameters: average 24-hour heart rate, 17.4 +/- 5.0%; maximum heart rate on Holter, 30.5 +/- 3.5%; heart rate during pharmacologic autonomic blockade, 32.7 +/- 3.5%; and maximum heart rate on isoproterenol, 23.1 +/- 4.6% (all p less than 0.01). Curves with pacemaker recovery time plotted against control cycle length remained unchan...
Healthcare leaders reject “damaging” denial that institutional racism exists
Authors: Gareth Iacobucci
Journal: BMJ (2021)

A controversial government commissioned review1 which found “no evidence of systemic or institutional racism” in the UK has been roundly criticised by healthcare leaders.

The review from the Commission on Race and Ethnic Disparities (CRED), published last week, was commissioned by the UK government to examine race relations in the UK in the wake of high covid-19 death rates in some ethnic minority groups and last year’s Black Lives Matter protests. But it has faced a fierce backlash after concluding that the UK is “no longer” a country where “the system is deliberately rigged against ethnic minorities.”

The commission, chaired by chief executive of educational charity Generating Genius Tony …
Prostaglandin E1 prevents increased lung microvascular permeability during intravascular complement activation in sheep.
Authors: M HGee, M VTahamont, J TFlynn, J WCox, R HPullen, N AAndreadis
Journal: Circulation Research (1987)

Prostaglandin E1 (PGE1) inhibits a variety of functions of activated neutrophils including respiratory burst, release of leukotriene B4, and adherence to endothelial cells. To determine if PGE, alters the pathophysiology of complement-induced lung vascular injury, experiments were conducted in anesthetized sheep with lung lymph fistulas given a 1-hour infusion of zymosan-activated plasma. PGE1 (30 ng/min/kg) or its saline vehicle was infused intravenously for 90 minutes beginning 30 minutes before the infusion of activated plasma. PGE1 had no effect on leukocyte count, the initial hypoxemia and thromboxane A2 release, or the development of acute pulmonary hypertension. However, PGE1 prevented steady-state increases in lung lymph flow that in vehicle-treated sheep signaled an increase in lung microvascular permeability. Furthermore, extraction of PGE1 by pulmonary endothelial cells was unaffected by the infusion of activated plasma. We propose that PGE1 prevented the increase in lung vascular permeability ...
Serial electrocardiograms in hypertensive cardiovascular disease.
Authors: R ADunn, R JZenner, H VPipberger
Journal: Circulation (1977)

A graphic method for depicting serial changes in electrocardiograms is described and demonstrated for patients being treated in an antihypertension clinic. For these patients, the diagnostic categories, normal, left ventricular hypertrophy, and biventricular hypertrophy, are of primary interest. For each electrocardiogram, 14 measurements are used to compute posterior probabilities for each of the three categories. A triangular grid is used to plot each set of probabilities for an electrocardiogram as one point, which by its position in the triangle can be related to the three categories simultaneously. Points representing successive electrocardiograms can be plotted in the same triangle, giving a pattern of change with time. This pattern of change has been corroborated with associated clinical information on a number of patients. This display, which can be produced quickly and efficiently on a computer graphics terminal, should be considered as a possible tool in evaluating the status of individual hyper...
Aetiology of appendicitis.
Authors: T L Cleave
Journal: BMJ (1979)

Aetiology of appendicitis SIR,-We read with interest the repeated assertion by Mr D P Burkitt and others that "the geographical distribution of appendicitis indicates that it is a disease associated with modern Western culture" (3 March, p 620).Reports, which often comprised moderately large series of cases of appendicitis, have recently been published from Africa,'-' South America,4 the Middle East,5-7 Malaysia,8 Indonesia,9 China,10 and even the Arctic."1The World Organisation of Gastroenterology re- search committee is conducting a large-scale multinational survey into the presentation of abdominal pain around the world.In every single centre, including Mexico City and Khon Kaen, Thailand, in large series of several hundred cases per centre, the commonest cause of admission to hospital with acute abdominal pain is acute appendicitis.It is not helpful therefore at the present time to equate appendicitis with modem Western culture.The relation between the two-if it exists at all-is undoubtedly far more complex than Mr Burkitt's simplistic assertion.
Effect of alpha-adrenergic stimulation on activation of protein kinase C and phosphorylation of proteins in intact rabbit hearts.
Authors: LTalosi, E GKranias
Journal: Circulation Research (1992)

The intracellular events and specifically the role of protein kinase C-mediated protein phosphorylation, after alpha-adrenergic receptor stimulation of the heart, are not well understood. We examined the phosphorylation of sarcolemmal, sarcoplasmic reticular, myofibrillar, and cytosolic proteins in perfused beating rabbit hearts on activation of protein kinase C by phenylephrine. Perfusion of rabbit hearts with phenylephrine was associated with a positive inotropic response, which was dose and time dependent. Maximal stimulation (1.54-fold increase in +dP/dt) was obtained with 10 microM phenylephrine at 4 minutes. Examination of the activity levels of protein kinase C in these hearts revealed a redistribution of this activity from the cytosolic to the membranous fraction, suggesting the activation of this enzyme in vivo. Prazosin, an alpha 1-adrenergic antagonist, prevented the increase in the inotropy and the redistribution of protein kinase C activity mediated by phenylephrine. Examination of the degree...
Inhibition of macrophage histone demethylase JMJD3 protects against abdominal aortic aneurysms
Authors: Frank M. Davis, Lam C. Tsoi, William J. Melvin, Aaron denDekker, Rachael Wasikowski, Amrita D. Joshi, Sonya Wolf, Andrea T. Obi, Allison C. Billi, Xianying Xing, Christopher Audu, Bethany B. Moore, Steven L. Kunkel, Alan Daugherty, Hong S. Lu, Johann E. Gudjonsson, Katherine A. Gallagher
Journal: The Journal of Experimental Medicine (2021)

Abdominal aortic aneurysms (AAAs) are a life-threatening disease for which there is a lack of effective therapy preventing aortic rupture. During AAA formation, pathological vascular remodeling is driven by macrophage infiltration, and the mechanisms regulating macrophage-mediated inflammation remain undefined. Recent evidence suggests that an epigenetic enzyme, JMJD3, plays a critical role in establishing macrophage phenotype. Using single-cell RNA sequencing of human AAA tissues, we identified increased JMJD3 in aortic monocyte/macrophages resulting in up-regulation of an inflammatory immune response. Mechanistically, we report that interferon-β regulates Jmjd3 expression via JAK/STAT and that JMJD3 induces NF-κB–mediated inflammatory gene transcription in infiltrating aortic macrophages. In vivo targeted inhibition of JMJD3 with myeloid-specific genetic depletion (JMJD3f/fLyz2Cre+) or pharmacological inhibition in the elastase or angiotensin II–induced AAA model preserved the repressive H3K27me3 on inflammatory gene promoters and markedly reduced AAA expansion and attenuated macrophage-mediated inflammation. Together, our findings suggest that cell-specific pharmacologic therapy targeting JMJD3 may be an effective intervention for AAA expansion.
Simulation studies of the electrocardiogram. I. The normal heart.
Authors: W TMiller, D BGeselowitz
Journal: Circulation Research (1978)

A digital computer model is presented for the simulation of the body surface electrocardiogram (ECG) during ventricular activation and recovery. The ventricles of the heart are represented in detail by a three-dimensional array of approximately 4000 points which is subdivided into 23 regions. Excitation sequence and cellular action potential data taken from the literature are used to determine the spatial distribution of intracellular potentials at each instant of time during a simulated cardiac cycle. The moment of the single dipole representing each region is determined by summing the spatial gradient of the intracellular potential distribution throughout the region. The resulting set of 23 dipoles is then used to calculate the potentials on the surface of a bounded homogeneous volume conductor with the shape of an adult torso. Simulated isopotential surface maps during both activation and recovery are in good agreement with data for humans reported in the literature.
Differences in cardiac calcium release channel (ryanodine receptor) expression in myocardium from patients with end-stage heart failure caused by ischemic versus dilated cardiomyopathy.
Authors: A MBrillantes, PAllen, TTakahashi, SIzumo, A RMarks
Journal: Circulation Research (1992)

The molecular basis for the systolic and diastolic dysfunction characteristic of end-stage heart failure in humans remains poorly understood. It has been proposed that both abnormal calcium handling and defects in the contractile apparatus may contribute to the myocardial dysfunction. Two channels, the calcium release channel (CRC) or ryanodine receptor of the sarcoplasmic reticulum (SR), and the slow calcium channel or dihydropyridine receptor (DHPR) of the transverse tubule, play key roles in regulating intracellular calcium concentration and in excitation-contraction (E-C) coupling in the heart. The DHPR serves as the voltage sensor and plasma membrane calcium channel resulting in activation of the CRC during E-C coupling in heart muscle. In this study, we investigated the levels of CRC expression in several forms of end-stage heart failure in humans. A cardiac CRC cDNA was cloned from rabbit and used as a probe for Northern blot analyses to determine mRNA levels in the left ventricles of normal (n = 4...
Efficacy, safety and tolerability of linezolid for the treatment of XDR-TB: a study in China
Authors: Catherine Berry, Tom A. Yates, James A. Seddon, Patrick P. J. Phillips, Philipp du Cros
Journal: European Respiratory Journal (2016)

Heterogeneity amongst cohorts of patients treated for drug-resistant tuberculosis (TB) make assessing the efficacy of new drugs and regimens unreliable without randomisation [1]. We warmly welcome the randomised controlled trial (RCT) "Efficacy, safety and tolerability of linezolid for the treatment of XDR-TB: a study in China" presented by Tang et al . [2]. Linezolid is now included on the WHO list of essential medicines [3] and falling prices will improve access. That Tang et al . [2] report a 35.3% absolute reduction in the risk of a poor outcome by adding linezolid to an optimised background regimen argues in favour of wider use. Linezolid remains a WHO "Group 5" drug, classifying it as an "anti-TB drug with limited data on efficacy and/or long term safety in the treatment of [drug-resistant]-TB" [4]. The limited data on the efficacy of drugs in this class has recently been reviewed [5]. These WHO classifications may shortly be revised and the exciting results from this study have the potential to alter guidance regarding the treatment of extensively drug-resistant (XDR) TB. We note the proposal to re-classify linezolid into Group 3 in an editorial in the October edition of the European Respiratory Journal [6]. It is with this in mind that we seek some clarifications. Response to the interesting RCT on linezolid for XDR-TB and request for information which may impact new guidelines <http://ow.ly/Z1dX5>
Programmed ventricular stimulation in survivors of an acute myocardial infarction.
Authors: DRoy, EMarchand, PThéroux, D DWaters, G BPelletier, M GBourassa
Journal: Circulation (1985)

The prognostic significance of programmed ventricular stimulation and its usefulness in relation to other forms of invasive and noninvasive testing was evaluated in 150 survivors of acute myocardial infarction. Ventricular tachyarrhythmias of 6 beats or more were induced in 35 (23%) patients. No significant differences existed between patients with inducible ventricular tachyarrhythmias and those without inducible ventricular tachycardia with respect to occurrence of spontaneous ventricular arrhythmias in the acute and early recovery phase of infarction or predischarge exercise-induced ischemia or arrhythmias, severity of coronary artery disease, or degree of left ventricular dysfunction. A higher incidence of inferior myocardial infarction was observed in patients with inducible ventricular tachycardia when compared with those without inducible ventricular tachycardia (66% vs 41%, p less than .01). During a mean follow-up of 10 +/- 5 months (range 2 to 19), there were two sudden deaths, three nonsudden d...
Abnormal vascular responses to supine exercise in hypertrophic cardiomyopathy.
Authors: P JCounihan, M PFrenneaux, D JWebb, W JMcKenna
Journal: Circulation (1991)

BACKGROUNDExercise hypotension has been documented in hypertrophic cardiomyopathy. It is not the result of an inability to augment cardiac output but instead relates to an inappropriate and exaggerated decrease in systemic vascular resistance at high work loads.METHODS AND RESULTSTo enable us to examine the behavior of the peripheral vasculature during exercise, 103 consecutive patients underwent maximal symptom-limited supine bicycle exercise with measurement of forearm blood flow. A minimum reduction of 12% from the basal value was defined as a normal response based on the study of 25 normal controls. In the patients, two patterns of forearm blood flow were observed. Sixty-four patients had an appropriate reduction in forearm blood flow of 40 +/- 16% from resting flow. In 39 patients, the forearm blood flow either failed to decrease or increased with exercise by 45 +/- 105% of the resting value. Patients with an abnormal forearm vasodilator response were younger (31 +/- 13 versus 46 +/- 14 years), and m...
Functional and autoradiographic evidence for endothelin 1 receptors on human and rat cardiac myocytes. Comparison with single smooth muscle cells.
Authors: C JMoody, M RDashwood, R MSykes, MChester, S MJones, M HYacoub, S EHarding
Journal: Circulation Research (1990)

This study aimed to determine whether receptors for endothelin were present on the cardiac myocyte as well as on vascular smooth muscle cells. Low- and high-resolution autoradiography was performed using 125I-endothelin 1 on intact rat myocardium and samples of human ventricle obtained from explanted hearts at the time of transplant. In addition to specific binding to the smooth muscle of the blood vessel lumen, there was considerable binding associated with cardiac myocytes. To discover whether there was any functional correlate for this binding, muscle cells were isolated enzymatically from human and rat ventricle and from rat femoral artery, and their contractile characteristics were studied. Single cardiac cells were superfused with physiological saline at 32 degrees C, and their length change was displayed continuously on a chart recorder. Endothelin 1 had a pronounced effect on shortening in both rat and human myocytes. The contraction amplitude was approximately doubled in both cases, from 4.1 +/- ...
Shall The Journal be Removed to Washington?
Authors: S. Laughton
Journal: JAMA (1891)

<h3>To the Editor:</h3> — I am opposed to the movement to change the place of publication of our National Journal from Chicago to the City of Washington. I think there is no valid reason for it:The Journalis ably conducted, centrally located geographically, and a large business city like Chicago is much more conducive to the support and advancement of a medical journal than<i>a political rookery</i>like the city of Washington. I think our western members would have just cause for complaint if it were removed farther East. Bangor, Me., March 15, 1891.