tbuckley/cabot-search huggingface dataset:
P109Opposite actions of atrial adenosine A1 receptor on G protein-coupled inwardly-rectifying potassium (GIRK/Kir3.1/3.4) and small Ca2+-activated K+ outward (KCa2/SK) currents
Authors: B Braganca, N Oliveira-Monteiro, S Nogueira-Marques, F Ferreirinha, PA Lima, PF Costa, M Faria, AP Fontes-Sousa, P Correia-De-Sa
Journal: Cardiovascular Research (2014)

Purpose: Adenosine fine-tuning regulates cardiovascular function. The negative chronotropic effect of adenosine depends on the activation of the most abundant adenosine receptor in the heart, the A1AR, leading to GIRK/Kir3.1/3.4 channels opening in the SA node. The A1AR-mediated responses in the atrial muscle also depend on KCa2/SK channel function (unpublished observations). Since these channels are involved in atrial repolarization and in human rhythm disturbances, we aimed at studying the interplay between A1AR and SK channels both in situ and single-cell preparations of rat atria. Methods: Isometric contraction experiments were performed on isolated spontaneously beating atria from Wistar rats. For whole-cell voltage-clamp recordings, atrial myocytes were enzymatically isolated by retrograde perfusion. Immunolocalization studies (A1AR, GIRK1, KCa2.2 and KCa2.3) were evaluated by confocal microscopy. The SA node was identified as a connexin-43 low / neurofilament-160 high immunoreactive region. Results: The selective A1AR agonist R-PIA (0.001-1μM) decreased atrial chronotropism and inotropism in concentration-dependent manner. However, the negative chronotropic effect of R-PIA (IC50~0.03 μM) was evidenced at much lower (~30 times) concentrations than the negative inotropic action (IC50~1 μM). Selective blockade of A1AR and of GIRK/Kir3.1/3.4 channels, respectively with DPCPX (100 nM) and tertiapin Q (300 nM), significantly attenuated the effects R-PIA. Blockade of KCa2/SK channels with apamin (30 nM) potentiated the negative inotropic response of R-PIA, without affecting atrial rate. Apamin-induced atrial sensitization to R-PIA was not observed with other cardiodepressant agents, namely oxotremorine (0.01-3 μM). Voltage-clamp experiments demonstrated that adenosine, via A1AR, plays a dual role in atrial cardiomyocytes by activating inwardly rectifying GIRK/Kir3.1/3.4 and inactivating outward Ca2+-activated KCa2/SK currents upon cell depolarization. Immunolabelling of A1AR, KIR3.1, KCa2.2 and KCa2.3 was observed throughout the right atria. Conclusion: Data demonstrate for the first time that A1AR has opposing effects on distinct K+ currents operating atrial repolarization. While A1AR activation favors the opening of inwardly rectifying GIRK/KIR3.1/3.4 channels modulating atrial automatism, it may also inactivate outward KCa2/SK currents. Taking into consideration that KCa2/SK channel dysfunction has pro-arrhythmic effects drugs targeting the A1AR for supraventricular tachycardia must be used with caution as they might precipitate atrial arrhythmias.
Ethics in Medicine: Historical Perspectlives and Contemporary Concerns
Authors: Lester S. King
Journal: JAMA (1978)

From the earliest days of medicine, medical ethics has been an important subject. The duties and obligations of the physician have received explicit attention for 2,500 years. However, since World War II there has been a sharply intensified interest, and in the past decade, in particular, ethical problems have aroused especial concern— manifested in many new publications, both journal articles and books.  This latest volume in the stream of publications is a massive anthology that starts with some of the Hippocratic corpus and includes publications that first appeared in 1977. The major emphasis rests on problems that are current, and the majority of the reprinted articles appeared originally in the 1970s, with a sprinkling of earlier works. Many of the publications are reprinted in their entirety; others are represented by generous excerpts.  The selections fall into seven divisions. The first is strictly historical; the second essentially philosophical. The others deal
Circulating <scp>microRNAs</scp> for predicting and monitoring response to mechanical circulatory support from a left ventricular assist device
Authors: Andrew C. Morley‐Smith, Adam Mills, Steven Jacobs, Bart Meyns, Filip Rega, André R. Simon, John R. Pepper, Alexander R. Lyon, Thomas Thum
Journal: European Journal of Heart Failure (2014)
PREVENTION OF PROGRESSION OF ABDOMINAL AORTIC ANEURYSM IN APOLIPOPROTEIN E-DEFICIENT MICE: ROLE OF PHOTOTHERAPY
Authors: S. David Gertz, Chen Rubinstein, Atilla Bulut, Yacov Berlatzky, Ronen Beeri, Dan Gilon, Leah Gavish, Mickey Harlev, Petachia Reissman, Lilach Gavish
Journal: Journal of the American College of Cardiology (2011)
Experimental Pulmonary Embolism
Authors: JOSEPH S. ALPERT, FLORENCE W. HAYNES, JAMES E. DALEN, LEWIS DEXTER
Journal: Circulation (1974)

Autologous blood clot was used to produce pulmonary macroembolism, and lycopodium spores to produce microembolism in normal mongrel dogs. Pressures were recorded from the pulmonary artery, left atrium and femoral artery; cardiac output and pulmonary blood volume (PBV) were determined using sequential indicator dilution curves from injections into the pulmonary artery and left atrium. Macro- and microembolism caused comparable elevations of pulmonary artery pressure and total pulmonary resistance. Macroembolism with blood clots resulted in marked decreases in PBV and pulmonary vascular compliance. However, microembolism with lycopodium spores caused only small decreases in PBV despite a large reduction in pulmonary vascular compliance. Prostaglandin E 1 infusion after microembolism had no effect on pulmonary hemodynamics, but caused significant systemic hypotension. After macroembolism PGE 1 infusion decreased PBV and decreased systemic arterial pressure.
Chemoprophylaxis of Tuberculosis: When Is the Benefit Worth the Risk and Cost?
Authors: THOMAS MOULDING
Journal: Annals of Internal Medicine (1971)

The number of persons in various risk categories who must be given isoniazid chemoprophylaxis to prevent one case of active tuberculosis has been estimated in order to help decide on indications for chemoprophylaxis. Assuming the protective effect of chemoprophylaxis is limited to 10 years, this number is 14.2 for persons with inactive cases of tuberculosis, 37.5 for primary tuberculosis in children, 81.3 for household contacts of active cases, 110.3 for tuberculin-positive adolescents with normal chest roentgenograms, and 163.4 for tuberculin-positive adults with normal chest roentgenograms. The cost to prevent one case in each of these categories is $824, $1,612, $813, $4,743, and $7,026, respectively. When weighing this information plus the knowledge of a significant but low frequency of isoniazid toxicity against the cost of treating an active case of tuberculosis and the complications of such treatment, a strong recommendation can be made to give preventive treatment to all cases of primary tuberculosis in children and all inactive cases of tuberculosis. By contrast, the justification for giving isoniazid to all tuberculin-positive adults with normal chest roentgenograms seems weak. In intermediate situations, such as all household contacts to persons with active disease, all tuberculin-positive adolescents with normal chest films, and selected tuberculinpositive adults with normal chest films who have additional conditions that increase the risk of developing active tuberculosis, chemoprophylaxis is probably justified unless isoniazid proves to be more toxic than is now established.
Surveillance for treatment failure of lentigo maligna with dermoscopy and<i>in vivo</i>confocal microscopy: new descriptors
Authors: P. Guitera, L.E. Haydu, S.W. Menzies, R.A. Scolyer, A. Hong, G.B. Fogarty, F. Gallardo, S. Segura
Journal: British Journal of Dermatology (2014)

Nonsurgical treatment (radiotherapy, imiquimod) is increasingly employed for the management of lentigo maligna (LM). While the diagnosis of LM remains difficult, the detection of treatment failure is even more challenging.To describe the sensitivity and specificity for the diagnosis of LM of individual features and methods using dermoscopy and in vivo reflectance confocal microscopy (RCM) to aid in the detection of treatment failure of LM following nonsurgical treatment.A retrospective study of dermoscopy and RCM images (blinded to the correlation with pathology) in patients with biopsy-confirmed LM who were undergoing nonsurgical treatment in two referral institutions - one in Sydney, Australia, and the other in Barcelona, Spain. Ninety-eight patients were treated nonsurgically for LM during the period 2006-2012. Thirty-one patients had abnormal dermoscopy or RCM evaluation, and had a biopsy that identified LM recurrence in 15 patients and nonmelanoma diagnoses in 16 patients (one Bowen disease, 15 solar changes).The diagnosis of treatment failure was difficult with dermoscopy, with a sensitivity of 80% and specificity of 56%, even with the interpretation of an expert. The best criterion was asymmetric hyperpigmented follicular openings, but this was present in only 47% of treatment failure LM. Isolated, very fine brown dots ('dust' appearance) correlated highly with the diagnosis of treatment failure LM (73% sensitivity and 88% specificity) and with pagetoid cells seen with RCM. The LM score, comprising six criteria, had a specificity of 94% and sensitivity of 100%.These methods and descriptors should help to manage the diagnosis of treatment failure.
Abstract 5397: Crocetin, a carotenoid compound derived from Saffron, enhances antitumor effects of paclitaxol and cisplatin in pancreatic cancer
Authors: Animesh Dhar, Peter S. Wiegmann, Greg Reed, William Gutheil, Peter Van Veldhuizen
Journal: Cancer Research (2010)

Abstract Pancreatic cancer is the fourth leading cause of cancer deaths in the United States and no significant treatment is at present available. Although there are an increasing number of therapeutic options available for patients with advanced disease, their efficacy is time limited and non-curative. Presently approximately 50-60% of cancer patients in the United States utilize therapies derived from plants, herbs, flowers, or nutrients (complementary and alternative medicine [CAM]), exclusively or concurrently with their traditional therapies such as chemotherapy or radiation therapy. One such CAM therapy is “crocetin”, a carotenoid compound isolated from the saffron plant. Recent studies demonstrated that crocetin has a significant antitumorigenic effect in both in vitro and in vivo on pancreatic cancer. Two conventional chemotherapeutic agents, paclitaxol (a microtubule-targeted agent) and cisplatin (a platinum based anticancer drug binds to DNA), have been demonstrated significant reduction of growth and proliferation in pancreatic cancer. Therefore, the aim of the series of experiments was to determine whether crocetin enhances paclitaxol or cisplatin induced proliferation in pancreatic cancer. MIA-PaCa-2 and BxPC3 cells were treated with crocetin and paclitaxol or cisplatin together at different doses and a proliferation assay was utilized using Click-it Edu flurorometric assay. Paclitaxol or cisplatin alone at higher doses (50-100nM) inhibited proliferation in both MIA PaCa2 and BxPC3 cells but crocetin (200μM) in combination of paclitaxol or cisplatin showed significant additive effect even at lower doses (10 and 25nM) of paclitaxol or cisplatin. The combinational effect is more pronounced in BxPC3 cells. Paclitaxol or cisplatin alone at higher doses (50-100nM) stimulated apoptosis using Deadend flurorometric TUNEL apoptosis assay in MIA PaCa2 and BxPC3 cells and apoptosis is more pronounced at lower doses in combination with crocetin. This study indicated that crocetin in combination with lower doses of paclitaxol or cisplatin inhibited proliferation and stimulated apoptosis in pancreatic cancer. The antitumorigenic effect is more pronounced in BxPC3 cells and paclitaxol is more effective than cisplatin at lower doses in combination with crocetin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5397.
Aetiology, diagnosis, investigation, and management of the cardiomyopathies
Authors: C. Oakley
Journal: BMJ (1997)

Aetiology, diagnosis, investigation, and management of the cardiomyopathies Celia OakleyCardiomyopathies are myocardial disorders that are not secondary to coronary disease or hypertension or to congenital, valvular, or pericardial abnormalities. 1 Classification is based on morphological and functional abnormalities, although overlap between groups is considerable.The four main types of cardiomyopathy are hypertrophic, dilated, restrictive, and arrhythmogenic right ventricular.Most heart muscle disorders affect mainly left ventricular structure and function, but the right ventricle is affected in arrhythmogenic right ventricular cardiomyopathy.
Head-to-Head Comparison of the Three Most Commonly Used Preoperative Models for Prediction of Biochemical Recurrence After Radical Prostatectomy
Authors: Giovanni Lughezzani, Lars Budäus, Hendrik Isbarn, Maxine Sun, Paul Perrotte, Alexander Haese, Felix K. Chun, Thorsten Schlomm, Thomas Steuber, Hans Heinzer, Hartwig Huland, Francesco Montorsi, Markus Graefen, Pierre I. Karakiewicz
Journal: European Urology (2009)
Repair of Transposition of the Great Arteries in 123 Pediatric Patients
Authors: GERARD L. CHAMPSAUR, DAVID M. SOKOL, GEORGE A. TRUSLER, WILLIAM T. MUSTARD
Journal: Circulation (1973)

From May 1963 to July 1972, 123 patients ranging in age from 20 days to 15 years, with D-transposition of the great arteries, underwent an intraatrial baffle operation using a pericardial baffle. They previously had had a total of 121 various palliative procedures. Twenty-six children (21%) died in the early postoperative period. The operative mortality was 13% in transposition of the great arteries with intact ventricular septum, 45% in trasnposition of the great arteries plus ventricular septal defect, and 33% in transposition of the great arteries plus ventricular septal defect and left ventricular outflow tract obstruction. By contrast the overall mortality has decreased to 15% in the 72 patients operated upon over the last 2 years. There were 12 late deaths, 10 of which occurred within the first year postoperatively. Unexplained heart failure accounted for four deaths. Two sudden deaths were attributed to arrhythmias. Three patients died of proven pulmonary venous obstruction, one of them at reoperation. Pulmonary hypertension, reoperation for detachment of the baffle, and hypoglycemia were each the cause of one late death. There were no proven cases of tricuspid incompetence. Eighty children have been repeatedly reexamined for up to 8 years and 6 months. The actuarial 6-year survival was 74.8% for survivors of operation. Seventy-three children were leading a normal life at the time of the report.
Cancer therapy and the randomized clinical trial: good medicine?
Authors: D. Kaufman
Journal: CA A Cancer Journal for Clinicians (1994)

True improvements in the treatment of cancer--by the introduction of new drugs or novel drug combinations, new therapeutic modalities, or technologic improvements of old modalities--result in higher response rates and prolonged survival when compared with existing therapies. When a new treatment convincingly meets the test of improving survival rates or, at worst, improving patients' quality of life, it becomes the accepted standard of care if its side effects are acceptable and its cost is not prohibitive. Improved therapeutic results can be demonstrated only by clinical trials with an adequate numbers of patients, appropriate control subjects, and a sufficient duration of follow-up. Therapeutic breakthroughs are revolutionary advances in treatment, usually rapidly and dramatically obvious in comparison with historic controls; demonstration of benefit in these cases does not usually require randomized trials. Much more common, however, are new therapies that represent modest, incremental advances over existing treatment and that usually require randomized comparison trials to demonstrate convincingly statistically significant improvement. A randomized clinical trial should test an important hypothesis. It must be carefully designed to ensure that both groups of patients are comparable in terms of various prognostic variables and to minimize subtle sources of bias. An honest belief that both arms of the trial are a priori equal must be maintained. Meeting these criteria, the randomized clinical trial offers to the individual cancer patient treatment that should be at least equal to the best available nonexperimental therapy. This equates with Good Medicine.
Recent Advances in Clinical Pathology. Series IV
Authors: Israel Davidsohn
Journal: JAMA (1965)

The first series was published in 1947, the second in 1951, and the third in 1960. Dr. Dyke defines clinical pathology as that field of medical activity covering the application, through the instrumentality of the hospital laboratory, of its basic sciences to the clinical practice of medicine both in the diagnosis and in the treatment of disease. In keeping with this definition, clinical pathology includes not only bacteriology, chemical pathology, hematology, and immunology, but also anatomic pathology.  Twenty-nine authors have contributed 25 chapters, dealing with anonymous mycobacteria, the Proteus-Providence group, tissue cultures in the diagnosis of respiratory virus infections, chemotherapy, sterilization, isoenzymes, inherited enzyme abnormalities, adrenal cortical and thyroid function tests, penicillamine therapy, hemoglobinopathies, plasma protein synthesis, fibrinolysis, hemolytic disease of the newborn, melanoma of the skin, bone biopsy, examination of the congenitally malformed heart and of the conduction system, and the neonatal pulmonary diseases.  A sign of changing trends
Alteration in vascular reactivity in isolated aortic rings from portal vein—constricted rats
Authors: Stelios Karatapanis, P. Aiden McCormickM.D.MRCP, Shilpa Kakad, Jason K. T. Chin, Mohammed Islam, Jamie Jeremy, David Harry, Neil McIntyre, Andrew K. Burroughs, Michael Jacobs
Journal: Hepatology (1994)

It has been suggested that increased production of nitric oxide by an inducible nitric oxide synthase isoenzyme is important in the pathogenesis of the vascular abnormalities seen in human beings and animals with portal hypertension. We investigated this hypothesis by studying the in vitro vascular reactivity of isolated aortic rings from portal vein—constricted and sham-operated rats. Aortic rings from portal vein—constricted rats exhibited significantly impaired contractility to phenylephrine and potassium chloride compared with control rats. Preincubation with the nitric oxide synthase inhibitor nitro-l-arginine methyl ester significantly increased contractility to phenylephrine and potassium chloride in both portal-hypertensive and control tissues, with greater effect in the portal-hypertensive rings. Despite nitro-l-arginine methyl ester, maximal contractions were still significantly smaller in the portal-hypertensive tissues. Vascular relaxation evoked by acetylcholine, but not by the endothelium-independent vasodilator glyceryltrinitrate, was significantly impaired in the portalhypertensive group. Our results demonstrate significant impairment in vascular function in aortic rings in this model of portal hypertension. The addition of a nitric oxide synthase inhibitor partly corrected these changes, suggesting that although nitric oxide is likely an important mediator, other factors may also be involved in the pathogenesis of these alterations in vascular function. (Hepatology 1994;20:1516-1521).
The CD45 tyrosine phosphatase regulates phosphotyrosine homeostasis and its loss reveals a novel pattern of late T cell receptor-induced Ca2+ oscillations.
Authors: S Volarević, B B Niklinska, C M Burns, H Yamada, C H June, F J Dumont, J D Ashwell
Journal: The Journal of Experimental Medicine (1992)

CD45 is a transmembrane tyrosine phosphatase implicated in T cell antigen receptor (TCR)-mediated activation. In T cell variants expressing progressively lower levels of CD45 (from normal to undetectable), CD45 expression was inversely related to spontaneous tyrosine phosphorylation of multiple proteins, including the TCR zeta chain, and was directly correlated with TCR-driven phosphoinositide hydrolysis. The Ca2+ response in these cells was altered in an unexpected fashion. Unlike wild-type cells, stimulated CD45- cell populations did not manifest an early increase in intracellular Ca2+, but did exhibit a delayed and gradual increase in mean intracellular Ca2+. Computer-aided fluorescence imaging of individual cells revealed that CD45- cells experienced late Ca2+ oscillations that were not blocked by removal of extracellular Ca2+. CD45 revertants had the signaling properties of wild-type cells. Thus, CD45 has a profound influence on both TCR-mediated signaling and phosphotyrosine homeostasis, and its loss reveals a novel role for this tyrosine phosphatase in Ca2+ regulation.
Depressed contractile state and increased myocardial consumption for non-mechanical work in patients with heart failure due to old myocardial infarction
Authors: Hideyuki Takaoka, Motoshi Takeuchi, Michio Odake, Katsuya Hata, Yoshihiko Hayashi, Masuki Mori, Mitsuhiro Yokoyama
Journal: Cardiovascular Research (1994)

Objective: The aim was to characterise the impaired myocardial mechanoenergetics in patients with heart failure due to old myocardial infarction by using the oxygen consumption versus left ventricular pressure – volume area (PVA) relationship. Methods: The o2-PVA relationship was assessed in 15 patients: group N consisted of seven patients with vasospastic angina pectoris whose left ventricular ejection fractions were normal [72(SD 8)%], and group F consisted of eight patients with old myocardial infarction whose left ventricular ejection fractions were reduced [45(11)%]. Left ventricular volume and pressure were measured by the conductance catheter method. o2was measured by thermodilution. Results: Linear o2-PVA relationships with dextran infusions were obtained in both groups (median r = 0.92 v 0.90). There was no difference in the slope between the two groups. There was a positive correlation between Emax and V̇o2 at median PVA (V̇o2.PVAO.8) in group N. Emax an index of left ventricular contractility, was significantly smaller in group F than in group N, at 5.1(2.1) v 3.2(1.1) mm Hg·ml−1·m2 p <0.05). On the other hand, the V̇o2 intercept in group F was comparable to that in group N, at 0.71(0.63) v 0.40(0.29) J·beat−1·100 g LV−1; NS). In addition, the ratio of V̇o2,PVA0.8 to Emax was significantly larger in group F than in group N: 0.55(0.14) v 0.89(0.37) J·beat−1·100 g LV−1·mm Hg−1ml·m−2 (p <0.05). Conclusions: These results suggest that the V̇o2 for non-mechanical work in group F is disproportionately high relative to the reduced contractility. An abnormality of excitation-contraction coupling rather than of crossbridge cycling may be responsible for the impaired mechanoenergetics in patients with heart failure due to old myocardial infarction. Cardiovascular Research 1994;28:1251-1257