tbuckley/cabot-search huggingface dataset:
Atrial Transmural Pressures during Experimental Pericardial Tamponade
Authors: GERHARD A. BRECHER, CHARLES A. GILBERT
Journal: Circulation Research (1971)

To elucidate the mechanism responsible for the occurrence of negative transmural atrial pressures in pericardial tamponade, saline or air was progressively injected into the pericardial sac. In 14 anesthetized, open-chest dogs, left atrial (LA), left ventricular (LV), and pericardial pressures (PP) were measured with catheter tip manometers. In beating and fibrillated hearts, measurements were carried out at normovolemia, hypovolemia and hypervolemia. Transmural atrial pressure (TAP = LA - PP) became negative when the PP reached 130 mm H 2 O whether the heart was beating or not. In normovolemia the relation between TAP and PP was: TAP (mm H 2 O) = 38.1--0.237PP--0.00042PP 2 . In anesthetized, closed-chest dogs, air inflation of pleural space produced pressures around the heart similar to those obtained in pericardial tamponade. With such pneumothorax, no negative TAP occurred either with beating or quiescent hearts. It is hypothesized that pericardial filling stiffens the pliable structures surrounding the heart and thereby diminishes the collapsibility of the atrial walls which form the inner part of the pericardial sac. Veins entering the atria through the filled pericardial sac are held open like the hole in an inflated inner tube. Through these mechanisms some cardiac filling is assured even with marked pericardial tamponade.
Preliminary Results of Ariel2, a Phase 2 Open-Label Study to Identify Ovarian Cancer Patients Likely to Respond to Rucaparib
Authors: I. McNeish, R. Coleman, A.M. Oza, G.E. Konecny, D. O'Malley, G. Kichenadasse, C. Scott, A. Oaknin, A. Floquet, D. Park, J. Brenton, K. Lin, S. Shetty, H. Giordano, M. Raponi, L. Rolfe, E. Swisher
Journal: Annals of Oncology (2014)
An Airway Wallstent for the treatment of tracheobronchial malignancies.
Authors: C T Bolliger, M Heitz, R Hauser, R Probst, A P Perruchoud
Journal: Thorax (1996)

BACKGROUND: The palliative effect of a new Airway Wallstent with a polyurethane covering was tested in patients with inoperable malignant lesions of the central airways. METHODS: Thirty six stents were inserted in 27 patients with obstruction (n = 24) or fistulae (n = 3), 15 of whom later received radiotherapy. The degree of symptom relief was assessed 1, 30, and 90 days after stent insertion. RESULTS: Stent deployment was successful in all patients. Significant improvements were observed one day after placement compared with before placement, with no change at 30 and 90 days, in dyspnoea index (mean (SD) 3.2 (0.7) before stent insertion compared with 1.8 (0.7) one day after insertion); Karnofsky index (32 (18) before insertion compared with 55 (15) one day after insertion); and obstruction of airway diameter (85 (11)% before insertion compared with 10 (12)% on day 1 after stent insertion). Stent-related complications needing later interventions included retained secretions (five patients), granuloma formation at ends of the stent (four patients), and stent migration (four patients). Over a median observation period of two months (range two days to 8.5 months) all stent coverings remained intact without delamination or tumour ingrowth. CONCLUSIONS: The Airway Wallstent provided excellent palliation for malignant obstructions and fistulae of the central airways. Retention of secretions and granuloma formation at the ends of the stent warrant minor technical improvements.
Symptomatic reflux disease: the present, the past and the future
Authors: Guy Boeckxstaens, Hashem B El-Serag, André J P M Smout, Peter J Kahrilas
Journal: Gut (2014)

The worldwide incidence of GORD and its complications is increasing along with the exponentially increasing problem of obesity. Of particular concern is the relationship between central adiposity and GORD complications, including oesophageal adenocarcinoma. Driven by progressive insight into the epidemiology and pathophysiology of GORD, the earlier belief that increased gastroesophageal reflux mainly results from one dominant mechanism has been replaced by acceptance that GORD is multifactorial. Instigating factors, such as obesity, age, genetics, pregnancy and trauma may all contribute to mechanical impairment of the oesophagogastric junction resulting in pathological reflux and accompanying syndromes. Progression of the disease by exacerbating and perpetuating factors such as obesity, neuromuscular dysfunction and oesophageal fibrosis ultimately lead to development of an overt hiatal hernia. The latter is now accepted as a central player, impacting on most mechanisms underlying gastroesophageal reflux (low sphincter pressure, transient lower oesophageal sphincter relaxation, oesophageal clearance and acid pocket position), explaining its association with more severe disease and mucosal damage. Since the introduction of proton pump inhibitors (PPI), clinical management of GORD has markedly changed, shifting the therapeutic challenge from mucosal healing to reduction of PPI-resistant symptoms. In parallel, it became clear that reflux symptoms may result from weakly acidic or non-acid reflux, insight that has triggered the search for new compounds or minimally invasive procedures to reduce all types of reflux. In summary, our view on GORD has evolved enormously compared to that of the past, and without doubt will impact on how to deal with GORD in the future.
Response to Letter Regarding Article, “Infarct Tissue Heterogeneity by Magnetic Resonance Imaging Identifies Enhanced Cardiac Arrhythmia Susceptibility in Patients With Left Ventricular Dysfunction”
Authors: André Schmidt, Clerio F. Azevedo, Alan Cheng, David A. Bluemke, Gary Gerstenblith, Robert G. Weiss, Eduardo Marbán, Gordon F. Tomaselli, João A.C. Lima, Katherine C. Wu, Sandeep N. Gupta, Thomas K. Foo
Journal: Circulation (2007)
FACILITIES FOR PSYCHIATRIC EDUCATION SURVEY OF PSYCHIATRIC DEPARTMENTS IN MEDICAL SCHOOLS
Authors: KENNETH E. APPEL, MANUEL M. PEARSON
Journal: American Journal of Psychiatry (1959)

1. There is great variation in support of psychiatric education and community service by medical school facilities. This ranges from superb with 17 full-time teachers, 100 to 200 beds in teaching hospitals, one-half to nearly a million dollars for research, and 40 residents at one medical center; to poor with no beds in a teaching hospital, no full-time men on the faculty, no funds for research, 7 to 20 thousand dollars hard money from the medical college to the department of psychiatry, and no residents. 2. Psychiatric education and medical education are not able to keep up with community demands for psychiatric treatment– the newer drugs notwithstanding. The responsibility for this is multiple: a small number of psychiatrists (10,000), much inadequate training in psychiatry for physicians in general, inadequate psychiatric leadership in many schools, deficient budgetary and space resources, negative attitudes toward psychiatry on the part of many medical men and administrators, inordinate claims of results compared with fulfillment in some areas of psychiatry, lack of community demands and support for better psychiatric education in many medical schools. 3. The lack of opportunities in many medical schools for adequate psychiatric training has in part led to: (a) the development of a demand for psychotherapy from non-medical people. (b) the development of psychoanalytic training outside of the medical schools. 4. In many schools, departmental and administrative functions swamp psychiatric leadership and creativity. 5. In many medical schools students are deprived of psychiatric knowledge and training important for the practice of medicine through lopsided medical training which disproportionately emphasizes the physical when a high proportion of the sick population are not classified as physical. 6. There is inadequate communication between departments of psychiatry throughout the country in respect to facilities, budgets, procedures and standards, including specific sources of income for staff members. 7. There is a general lack of information concerning the overall aspects of medical education and the proportionate part of this borne by departments of psychiatry. 8. Medical schools which have participated in this survey now have available to them comparative information regarding their own facilities and those of other departments. 9. Research activities and budgets in departments of psychiatry vary greatly from none to outstanding programs. 10. Finally, this study suggests the desirability that teachers, educational directors and medical school administrators come together for conference to discuss medical education, psychiatric education and training, and community service in which billions of dollars are involved.
Role of K <sub>ATP</sub> Channels in the Maintenance of Ventricular Fibrillation in Cardiomyopathic Human Hearts
Authors: Talha A. Farid, Krishnakumar Nair, Stephéne Massé, Mohammed Ali Azam, Ange Maguy, Patrick F. H. Lai, Karthikeyan Umapathy, Paul Dorian, Vijay Chauhan, András Varró, Abdul Al-Hesayen, Menashe Waxman, Stanley Nattel, Kumaraswamy Nanthakumar
Journal: Circulation Research (2011)

Ventricular fibrillation (VF) leads to global ischemia. The modulation of ischemia-dependent pathways may alter the electrophysiological evolution of VF.We addressed the hypotheses that there is regional disease-related expression of K(ATP) channels in human cardiomyopathic hearts and that K(ATP) channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness.In a human Langendorff model, electric mapping of 6 control and 9 treatment (10 μmol/L glibenclamide) isolated cardiomyopathic hearts was performed. Spontaneous defibrillation was studied and mean VF cycle length was compared regionally at VF onset and after 180 seconds between control and treatment groups. K(ATP) subunit gene expression was compared between LV endocardium versus epicardium in myopathic hearts. Spontaneous VF termination occurred in 1 of 6 control hearts and 7 of 8 glibenclamide-treated hearts (P=0.026). After 180 seconds of ischemia, a transmural dispersion in VF cycle length was observed between epicardium and endocardium (P=0.001), which was attenuated by glibenclamide. There was greater gene expression of all K(ATP) subunit on the endocardium compared with the epicardium (P<0.02). In an ischemic rat heart model, transmural dispersion of refractoriness (ΔERP(Transmural)=ERP(Epicardium)-ERP(Endocardium)) was verified with pacing protocols. ΔERP(Transmural) in control was 5 ± 2 ms and increased to 36 ± 5 ms with ischemia. This effect was greatly attenuated by glibenclamide (ΔERP(Transmural) for glibenclamide+ischemia=4.9 ± 4 ms, P=0.019 versus control ischemia).K(ATP) channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of K(ATP) channels promotes spontaneous defibrillation in cardiomyopathic human hearts by attenuating the ischemia-dependent spatiotemporal heterogeneity of refractoriness during early VF.
Osteoarticular complications of brucellosis.
Authors: J D Colmenero, J M Reguera, A Fernandez-Nebro, F Cabrera-Franquelo
Journal: Annals of the Rheumatic Diseases (1991)

Two hundred and sixty three patients with a diagnosis of brucellosis between January 1984 and December 1987 were studied prospectively. Sixty five patients (25%) developed osteoarticular complications. These patients had a more prolonged course than those with no complications. Spondylitis in 38 (58%) and sacroiliitis in 29 (45%) were the most prevalent. There were no significant laboratory, serological, or bacteriological differences between patients with and without osteoarticular complications. At diagnosis 47 patients (72%) showed radiographic abnormalities, commonly in axial sites but rarely in peripheral sites. Radionuclide bone scan was positive with no radiographic abnormalities in 17 (26%) of cases. Fifty seven patients received medical treatment alone, 51 (89%) being cured with a single course of treatment. Treatment failed or there was a relapse in six patients (11%), of whom five had spondylitis. Eight of the 65 patients (12%), all of whom had spondylitis and paravertebral or epidural abscesses, also required surgical treatment.
Dysphagia in lung cancer
Authors: R. Amin
Journal: Journal of the Royal Society of Medicine (2002)

In his discussion of paraneoplastic conditions causing dysphagia Dr Camidge does not include paraneoplastic hypercalcaemia (November 2001 JRSM, pp. 567-572). In the hospital population, hypercalcaemia is a common metabolic complication of malignancy. Hypercalcaemia has several recognized effects on the gastrointestinal system, and dysphagia has occasionally been reported1,2. Muscular weakness is a prominent feature which can seem paradoxical from a physiological point of view since calcium ions are responsible for the excitation—contraction coupling in all muscle cells. Calcium ions are involved in neuromuscular transmission and muscular contractions. At the neuromuscular junction, release of acetylcholine is stimulated by the rapid influx of calcium ions into the synapse. In all types of muscle a rise in intracellular calcium promotes contraction. In skeletal muscle, it stimulates interactions between actin and myosin by removing the inhibitory influence of the troponin—tropomyosin complex. In smooth muscle, calcium ions bind to calmodulin which, via activation of a protein kinase, phosphorylates myosin. This phosphorylation is a prerequisite for activation of the actin—myosin complex which leads to muscular contraction. Hypercalcaemia reduces the contractility of smooth muscle, which may explain the pathogenesis of dysphagia in patients with hypercalcaemia.
The PROGRESS trial three years later: time for more action, less distraction
Authors: Stephen MacMahon, Bruce Neal, Anthony Rodgers, John Chalmers
Journal: BMJ (2004)

Since the publication of the results of the PROGRESS trial, there has been much comment in the BMJ and elsewhere.1 2 Most of this acknowledges the importance of the findings for the care of patients with cerebrovascular disease. These patients are at high risk of stroke recurrence, and before the trial was completed few interventions had been proved to reduce this risk. Aspirin was known to modestly reduce the risk of recurrence of ischaemic stroke, but no treatment had been shown to reduce the frequently catastrophic recurrence of cerebral haemorrhage. This situation was changed profoundly by the results of PROGRESS, which showed that a simple blood pressure lowering regimen substantially reduced the risks of recurrent stroke,3 disability,4 and cardiac events5 across a broad range of blood pressure levels in patients with either ischaemic or haemorrhagic cerebrovascular disease.

PROGRESS was conceived during an era in which many stroke specialists were concerned about possible risks of blood pressure lowering in patients with compromised cerebral circulation. While epidemiological evidence indicated that the lowest blood pressure levels were associated with the lowest risks of stroke recurrence,6 prevailing clinical opinion required us to allow individual doctors the discretion to determine the intensity of the blood pressure lowering regimen they provided to individual patients. …
Involvement of calcitonin gene–related peptide in the modulation of human myometrial contractility during pregnancy
Authors: Yuan-Lin Dong, Li Fang, Sudhir Kondapaka, Pandu R. Gangula, Sunil J. Wimalawansa, Chandrasekhar Yallampalli
Journal: Journal of Clinical Investigation (1999)

Calcitonin gene–related peptide (CGRP) is a potent vasodilator and relaxes smooth muscle of a variety of tissues, but the effects of CGRP on human myometrial contractions and the changes in CGRP receptors (CGRP-Rs) in human myometrium have not been described. We report that CGRP induced dose-dependent relaxation in spontaneously contracting myometrium from pregnant women. This relaxation effect is diminished in myometrium obtained from patients during labor and in the nonpregnant state. CGRP-induced relaxations are inhibited by a CGRP-R antagonist (CGRP8-37), a soluble guanylate cyclase inhibitor (LY83583), and a nitric oxide synthase inhibitor (L-NAME). Both Western blotting and mRNA analysis showed that CGRP-Rs are present in human myometrium, and that the expression of these receptors is increased during pregnancy and decreased during term labor. Immunofluorescent staining revealed that CGRP-Rs are abundant in the myometrial cells of pregnant women who are not in labor, and are minimal in uterine specimens from women in labor and in the nonpregnant state. We conclude that increased CGRP-Rs in myometrium, and resulting enhanced myometrial sensitivity to CGRP, may play a role in maintaining human myometrium in a quiescent state during pregnancy, and that a decline in the CGRP-Rs at term could contribute to the initiation of labor.
Pulmonary manifestations of immunoglobulin G4-related sclerosing disease
Authors: J.H. Ryu, H. Sekiguchi, E.S. Yi
Journal: European Respiratory Journal (2011)

Immunoglobulin (Ig)G4-related sclerosing disease (ISD) (also called IgG4-related systemic disease, IgG4-related disease or hyper-IgG4 disease) is a recently described systemic fibroinflammatory disease associated with elevated circulating levels of IgG4. Although initial descriptions of this disorder focused on its pancreatic presentation (autoimmune pancreatitis), it has become apparent that ISD is a systemic disease with many facets. The lesion of ISD is characterised by lymphoplasmacytic inflammation, fibrosis, phlebitis and increased numbers of IgG4-positive plasma cells. The disease can either be localised to one or two organs, or be present with diffuse multi-organ disease. Furthermore, lesions in different organs can present simultaneously or metachronously. In the thorax, lesions associated with ISD have been described in the lung parenchyma, airways and pleura, as well as the mediastinum. Data published to date suggest that ISD may account for a portion of various fibroinflammatory conditions of unknown cause encountered in the chest, including inflammatory pseudotumours, idiopathic interstitial pneumonias, fibrosing mediastinitis, inflammatory pleural lesions and, occasionally, airway disease. Some aspects of pulmonary manifestations attributed to ISD remain controversial and additional studies are needed to clarify the relationship along with the increasing relevance of this disorder to pulmonary medicine.
Transient Effect of Inhaled Fluticasone on Airway Mucosal Blood Flow in Subjects with and without Asthma
Authors: SUNIL D. KUMAR, JORGE L. BRIEVA, IGNACIO DANTA, ADAM WANNER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Topically applied glucocorticosteroids (GS) have been shown to cause local vasoconstriction in normal skin and this phenomenon is commonly used to assess the potency of topical GS (McKenzie skin blanching test). The purpose of the present study was to determine if an inhaled GS, fluticasone propionate (FP), similarly leads to vasoconstriction in the airway mucosa and if subjects with and without asthma have differential vascular responsiveness to GS. In 10 nonsmokers with stable asthma and 10 nonasthmatic nonsmokers, airway mucosal blood flow (Q˙aw) expressed per milliliter of anatomical dead space and the forced expiratory volume in 1 s (FEV 1) were determined before and serially after inhalation of FP (88 to 1,760 μ g) or placebo. Baseline mean ( ± SE) Q˙aw was 55.1 ± 1.0 and 44.2 ± 1.1 μ l · min− 1 · ml− 1 in subjects with and without asthma, respectively (p < 0.001). The corresponding mean FEV1 values were 2.34 ± 0.13 and 3.22 ± 0.12 L (p < 0.001). FP at 880 μ g but not placebo produced a transient decrease in mean Q˙aw with a nadir at 30 min and return toward baseline at 90 min postinhalation; the maximum mean decrease was 37% in subjects with asthma and 21% in unaffected subjects (p < 0.01); 880 μ g of FP was the lowest effective dose. FEV1 did not change after FP administration in either group. These results demonstrate a transient vasoconstrictive action of inhaled FP in the airway mucosa, with a greater vascular responsiveness in subjects with asthma than in unaffected subjects. The measurement of Q˙aw may provide a more relevant means of assessing the potency of inhaled GS than the McKenzie skin blanching test. In addition, our observation suggests that inhaled GS have potentially beneficial effects in asthma that is not related to their antiinflammatory action. Kumar SD, Brieva JL, Danta I, Wanner A. Transient effect of inhaled fluticasone on airway mucosal blood flow in subjects with and without asthma.
Regulation of Immune Responses by mTOR
Authors: Jonathan D. Powell, Kristen N. Pollizzi, Emily B. Heikamp, Maureen R. Horton
Journal: Annual Review of Immunology (2012)

mTOR is an evolutionarily conserved serine/threonine kinase that plays a central role in integrating environmental cues in the form of growth factors, amino acids, and energy. In the study of the immune system, mTOR is emerging as a critical regulator of immune function because of its role in sensing and integrating cues from the immune microenvironment. With the greater appreciation of cellular metabolism as an important regulator of immune cell function, mTOR is proving to be a vital link between immune function and metabolism. In this review, we discuss the ability of mTOR to direct the adaptive immune response. Specifically, we focus on the role of mTOR in promoting differentiation, activation, and function in T cells, B cells, and antigen-presenting cells.
Differential Protein Kinase C Isoform Regulation and Increased Constitutive Activity of Acetylcholine-Regulated Potassium Channels in Atrial Remodeling
Authors: Samy Makary, Niels Voigt, Ange Maguy, Reza Wakili, Kunihiro Nishida, Masahide Harada, Dobromir Dobrev, Stanley Nattel
Journal: Circulation Research (2011)

Atrial fibrillation (AF) causes atrial-tachycardia remodeling (ATR), with enhanced constitutive acetylcholine-regulated K+ current (I(KAChC)) contributing to action potential duration shortening and AF promotion. The underlying mechanisms are unknown.To evaluate the role of protein-kinase C (PKC) isoforms in ATR-induced I(KAChC) activation.Cells from ATR-dogs (400-bpm atrial pacing for 1 week) were compared to control dog cells. In vitro tachypaced (TP; 3 Hz) canine atrial cardiomyocytes were compared to parallel 1-Hz paced cells. I(KAChC) single-channel activity was assessed in cell-attached and cell-free (inside-out) patches. Protein expression was assessed by immunoblot. In vitro TP activated I(KAChC), mimicking effects of in vivo ATR. Discrepant effects of PKC activation and inhibition between control and ATR cells suggested isoform-selective effects and altered PKC isoform distribution. Conventional PKC isoforms (cPKC; including PKCα) inhibited, whereas novel isoforms (including PKCε) enhanced, acetylcholine-regulated K+ current (I(KACh)) in inside-out patches. TP and ATR downregulated PKCα (by 33% and 37%, respectively) and caused membrane translocation of PKCε, switching PKC predominance to the stimulatory novel isoform. TP increased [Ca2+]i at 2 hours by 30%, with return to baseline at 24 hours. Buffering [Ca2+]i during TP with the cell-permeable Ca2+ chelator BAPTA-AM (1 μmol/L) or inhibiting the Ca2+-dependent protease calpain with PD150606 (20 μmol/L) prevented PKCα downregulation and TP enhancement of I(KAChC). PKCε inhibition with a cell-permeable peptide inhibitor suppressed TP/ATR-induced I(KAChC) activation, whereas cPKC inhibition enhanced I(KAChC) activity in 1-Hz cells.PKC isoforms differentially modulate I(KACh), with conventional Ca(2+)-dependent isoforms inhibiting and novel isoforms enhancing activity. ATR causes a rate-dependent PKC isoform switch, with Ca2+/calpain-dependent downregulation of inhibitory PKCα and membrane translocation of stimulatory PKCε, enhancing I(KAChC). These findings provide novel insights into mechanisms underlying I(KAChC) dysregulation in AF.