tbuckley/cabot-search huggingface dataset:
Abstract 2575: Mechanisms Underlying Activation of Constitutive Acetylcholine-regulated Potassium Channels by Atrial Tachycardia Remodeling
Authors: Samy Makary, Ange Maguy, Reza Wakili, Niels Voigt, Kunihiro Nishida, Dobromir Dobrev, Stanley Nattel
Journal: Circulation (2009)

Background: Atrial tachycardia remodeling (ATR) enhances constitutive acetylcholine regulated K+ current (IKAChC), which causes APD shortening and AF promotion. The underlying molecular mechanisms are unknown. Here we examined the role of G-proteins and regulation by classical Ca2+-dependent PKC (cPKC) and novel (nPKC) isoforms. Methods: Cell-attached single-channel IKACh was recorded with carbachol (10 μM) in the pipette (agonist-activated current, IKAChA) and in its absence (IKAChC) in atrial cells from control (CTL) and ATR (400 bpm × 1 wk) dogs. Results: ATR increased IKAChC opening frequency (fo) from 2.2±0.2 to 15.3±0.6 Hz (figure). The Gβγ-scavenger M119 inhibited IKAChC similarly for CTL and ATR (by 67±2%, 65±1%), and more than IKAChA (by 27±2%). Combined cPKC/nPKC inhibition with BIM-I enhanced IKAChA (by 14±3%) but suppressed ATR-IKAChC (by 35±5%), suggesting stimulatory effects of some PKC isoforms and inhibitory effects of others. Selective inhibition of cPKC with GO-6976 had no effect on IKA...
Abstract B72: Developing drug combinations to co-target pancreatic cancer and its supporting stroma
Authors: Elisabete Florencio Carapuça, Emilios Gemenetzidis, Christine Feig, David Tuveson, Hemant Kocher
Journal: Cancer Research (2015)

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an intense desmoplastic stroma, due to the activation of pancreatic stellate cells (PSC). The activated PSC are characterized by a reduction of fat droplets, expression of α-smooth muscle actin (α-SMA), and an increased synthesis and secretion of several connective tissue components such as fibronectin (FN) and collagen type I. Aberrant stromal-epithelial interactions contribute to pancreatic cancer spread and metastasis raising the possibility that targeting the stroma may represent viable strategy for treating pancreatic cancer. Our group has shown that pancreatic cancer progression can be restrained via modulation of the stellate cells in the stroma. Methods: Organotypic cultures (OT) were constructed to mimic human PDAC. Treatment of OT was performed to mimic human chemotherapy regimen cycles with all-trans retinoic acid (ATRA), targeting PSC, and the chemotherapeutic agent Gemcitabine (GEM), targeting pancreatic cancer cells (PCC). Furthermore, KPC mice (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre) were treated with the combination of GEM and ATRA. Appropriate controls were used for both in vivo and in vitro assays using either drug alone or vehicle alone to dissect effect of individual drug. Both in vivo and in vitro assays were studied for various surrogate endpoints for chemotherapy efficacy. Results:In the organotypic model, ATRA alone or in combination with GEM reduced cancer cell and stellate cell invasion. The same treatment also reduced cancer cell proliferation. Stellate cell activation, as measured by fibronectin production per stellate cell, was significantly reduced upon combination treatment with GEM/ATRA, in comparison to cultures treated with GEM or ATRA only. In the KPC mice model, ATRA alone or in combination with GEM caused stromal collapse. The same regimen treatment led to an increase in vascular density in the tumor area and a significant impairment of the tumor growth, when compared with mice treated with ATRA or GEM alone. The number of necrotic areas was also higher in tumors from mice treated with the combination treatment of GEM/ATRA. Further assessments are being carried out. Conclusions:The combination treatment of all-trans retinoic acid and Gemcitabine may have a synergistic detrimental effect upon pancreatic cancer progression. Citation Format: Elisabete Florencio Carapuça, Emilios Gemenetzidis, Christine Feig, David Tuveson, Hemant Kocher. Developing drug combinations to co-target pancreatic cancer and its supporting stroma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B72.
Urgency and priority models
Authors: I. M Mitchell, D. W Quinn, P. Wraighte, W. Rhoden, G. Cooper
Journal: BMJ (1998)

Editor—The recent interest in priority scoring for surgical operations is to be commended. The paper by the Northern Ireland Clinical Resource Efficiency Support Team highlights the differences between “urgency” and “priority” and how demographic and lifestyle related details may influence the timing of coronary artery bypass surgery.1 Unfortunately this model has limited practical application. 

Firstly, although the opinion of the referring doctor is important, the ultimate responsibility for prioritising the waiting list lies with the cardiac surgeons, who represented only a minority of the judges (4 out of 33). Furthermore, the study does not take into account how cardiac surgeons organise their waiting lists. Some run their list individually and some operate a joint waiting list; most would separate the list into emergency, urgent, and routine cases, but few would adopt a more sophisticated priority system within each group. This is not to say such an approach would be wrong, but it would imply a constant reshuffling of patients as the list grew and would make it impossible to give patients a reasonable estimate of their wait. 

Secondly, inspection of the angiogram is an integral part of patient assessment, but this was denied to the judges in this study. Simply recording the number of severely diseased vessels fails to take into account the importance of the anatomical location of the stenoses, the dominance of the coronary vessels, and their relative size. A stenosis of the proximal left anterior descending artery in association with a tight proximal circumflex stenosis would be assigned more urgency and priority than perhaps a stenosis of the distal left anterior descending artery in combination with disease in the posterior descending artery—yet both are examples of two vessel disease. This point is particularly identified in a study from New Zealand.2

Finally, the success of interventional cardiology creates an increasing number of grey areas. The option to treat surgically or by endovascular intervention may be biased by the relative length of the waiting list for each technique and by the patient’s own wishes, as much as by the clinical need for intervention. 

Although the model presented allows those deciding about waiting lists some insights into how others view the surgical treatment of coronary artery disease, the decisions made were based on insufficient clinical data and may not reflect current practice. Unfortunately, this model also fails to recognise the key role of the cardiac surgeon as the “gate keeper” of the waiting list.
Neurogenic and hysterical seizures in children and adolescents: differential diagnostic and therapeutic considerations
Authors: D T Williams, H Spiegel, D I Mostofsky
Journal: American Journal of Psychiatry (1978)

For patients whose seizures are not controlled by medication alone, psychotherapeutic intervention can sometimes play a useful adjunctive role in both differential diagnosis and treatment. Diagnostic issues include the differentiation between neurogenic and hysterical seizures as well as the delineation of the possible role of psychogenic stress in triggering neurogenic seizures. Therapeutic considerations focus on the alleviation of precipitating stresses as well as the development of a sense of mastery in the patient.
Abstract 1370: Bcl-2 Regulation of Sarco/Endoplasmic Reticulum Calcium Stores Mediates the Autophagic Response to Nutrient Deprivation in the HL-1 Cardiomyocyte
Authors: Nathan R Brady, Anne Hamacher-Brady, Roberta A Gottlieb
Journal: Circulation (2006)

Apoptotic and autophagic pathways are linked through the interaction of anti-apoptotic Bcl-2 proteins with the autophagy protein Beclin1. However, the nature of the interaction, either in promoting...
Comparison of physiological impairment in ILD patients with and without diagnostic IPF features
Authors: Beatrice Anne Marie Downie, Joanna Shakespeare, Lynsey Archer, Robert Hastings, Felix Woodhead, Emma Helm, Rhian Hughes, David Parr
Journal: European Respiratory Journal (2014)

Introduction   Physiological impairment correlates with outcome in interstitial lung diseases (ILD), which is known to be worse in patients with idiopathic pulmonary fibrosis (IPF), but the role of cardiopulmonary exercise testing (CPET) is less well established than pulmonary function tests.   Objectives   To compare physiological impairment in ILD patients with and without diagnostic features of IPF using static lung function, incremental shuttle walk and CPET.   Methods   46 patients were recruited from a specialist ILD clinic. Disease classification into 9IPF9 or 9not diagnostic of IPF9 (nd-IPF) using the ATS/ERS 2011 guidelines was achieved by MDT consensus (Raghu, G.  et al . Am J Respir Crit Care Med, 2011; 183(6):788-824).  Comparison of resting and exercise parameter means was with Mann-Whitney, Chi-squared, Fisher9s exact and unpaired t-tests.   Results   24 patients were designated IPF and 22 as nd-IPF. The IPF group was 92% male, and the nd-IPF group was 54% male (p = 0.0065). RV (% predicted) was higher in the nd-IPF group (47% vs. 38%, p = 0.02), but there were no other significant differences.  All IPF patients and 19 nd-IPF patients reached anaerobic threshold (AT). The ventilatory equivalent for carbon dioxide (VE/VC02) at AT in the IPF group was 38.12 compared with 34.23 in the nd-IPF group (p = 0.057).   Conclusion   Despite differences in the prognosis of these ILD subgroups, our data shows similar physiology at presentation. This suggests a common pathophysiological mechanism and, possibly, a common symptom threshold that leads to clinical presentation.
Abstract 6052: Sustained Release of Platelet-Rich Plasma, Cocktail of Potent Angiogenic Cytokines, Restores Blood Perfusion by Recruitment of Bone Marrow Derived Haematopoietic Stem Cells in the Mouse Hind Limb Ischemia
Authors: Shyamal Bir, Akira Marui, Jiro Esaki, Kenichi Yamahara, Hideki Tsubota, Masatoshi Fujita, Yasuhiko Tabata, Tadashi Ikeda
Journal: Circulation (2008)
Improved oral fenretinide delivery with novel Lym-X-Sorb™ organized lipid complex
Authors: B. J. Maurer, T. Frgala, B. C. Sun, J. Vlckova, C. P. Reynolds, D. W. Yesair, S. W. Burgess, R. T. McKee, W. A. Shaw
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

642 

High-dose oral N-(4-hydroxyphenyl)retinamide (fenretinide, 4-HPR) is in phase II clinical trials in neuroblastoma, prostate, and ovarian cancers. However, in phase I trials, the limited bioavailability of the current 4-HPR capsule formulation caused high inter-patient variation in plasma levels and decreased patient compliance (due to the large number of capsules consumed). To improve the oral delivery of 4-HPR, and possibly increase plasma and tissue levels, 4-HPR was complexed with the novel lipid matrix Lym-X-Sorb™ (LXS). LXS is an organized lipid matrix of lysophosphatidylcholine, monoglyceride and fatty acid that enfolds drug in acyl-constituents of LXS monomer backbones for absorbtion in the proximal intestinal. The LXS monomers form chylomicron-like elements and enter systemic circulation via the thoracic duct. Earlier single-dose studies of oral LXS/4-HPR complexes in dogs and humans demonstrated improved plasma concentrations of 4-HPR compared to the current capsule. At equal doses, the LXS/4-HPR complex obtained a four-fold peak plasma increase in dogs. In humans, equivalent peak plasma concentrations were obtained using LXS/4-HPR at 20% of the capsular dose. In the present work, BALB/c mice were fed doses of 120, 250, or 560 mg/kg/day of LXS/4-HPR complex, expelled 4-HPR capsule contents, or expelled capsule contents mixed with an equivalent of 10 oz of vegetable oil per day. Four LXS formulations were examined; two formulations were also mixed with a soy-based nutritional supplement, or water. Mice were treated BID for 4.5 days and sacrificed 3 hours post treatment. 4-HPR levels were assayed by HPLC in plasma, liver, lung, kidney, and brain. Results demonstrated LXS/4-HPR complexes obtained higher plasma and tissue levels compared to the capsular formulation. At least one LXS/4HPR formulation increased 4-HPR levels: 1) At 120 mg/kg/day, in plasma, 2.5-fold (P<0.01); in liver, 2-fold (P<0.02); in lung, 2-fold (P<0.03); in kidney, 2-fold (P<0.01); in brain, 3-fold (P<0.01) 2) At 250 mg/kg/day, in plasma, 3-fold (P<0.01); in liver, 4-fold (P<0.01); in lung, 3-fold (P<0.04); in kidney, 8-fold (P<0.02); in brain, 4-fold (P=0.11) 3) At 560 mg/kg/day (single animal results), in plasma, 4-fold; in liver, 5-fold; in lung, 7-fold; in kidney, 1.5-fold; in brain, 2-fold. We conclude that LXS/4-HPR formulations have the potential to improve the oral delivery of high-dose 4-HPR. Phase I trials of an oral powdered LXS/4-HPR formulation in pediatric and adult cancer patients are planned for 2004.
Renal metabolic response to acid base changes
Authors: George A. O. Alleyne, George H. Scullard
Journal: Journal of Clinical Investigation (1969)

Experiments were done on rats to investigate the nature of the renal response to metabolic acidosis and the changes in enzyme activity associated with increased ammoniagenesis. When metabolic acidosis was induced with oral feeding of ammonium chloride for 48 hr, there was an increase of activity of the enzyme phosphoenolpyruvate carboxykinase (PEPCK) in whole kidneys as well as in the kidney cortex. There was no change in PEPCK in liver, and glucose-6-phosphatase showed no change in kidney or liver in response to metabolic acidosis. The increase in PEPCK activity in kidney cortex varied with the degree of acidosis and there was a close correlation between cortical PEPCK activity and urinary ammonia. Kidney cortex mitochondrial PEPCK did not change in response to metabolic acidosis. An increase in PEPCK occurred as early as 6 hr after NH(4)Cl feeding, before there was any increase in kidney glutaminase I activity. Rats fed sodium phosphate, or given triamcinolone intramuscularly, developed a metabolic alkalosis, but there was increased urinary ammonia and an increase in activity of renal cortical PEPCK. Triamcinolone plus ammonium chloride induced a greater increase of PEPCK activity than triamcinolone by itself; on the contrary, the rise of glucose-6-phosphatase induced by triamcinolone was not enhanced by acidosis. Glucose-6-phosphatase from control and acidotic rats had identical kinetic characteristics. The results indicate that increased PEPCK activity is constantly related to increases of urinary ammonia. It is proposed that the increase of PEPCK activity is the key event in the ammoniagenesis and gluconeogenesis which follow on metabolic acidosis.
别忽略了"早孕"的诊断
Authors: 周仲华
Journal: BMJ (2007)

“早孕”能被漏诊吗？你一定会说诊断早孕很容易呀，现在早早孕试纸很普及，价格便宜、应用方便，检验的灵敏度和特异度又很高，怎么可能轻易被忽略呢？可是，在临床上我发现，如果病人直接以“停经”或“要求检查是否怀孕”为主诉来诊的，或者是直接就诊于妇产科医生，一般都会得到及时正确的诊断，因为妇产科医生很容易想到自己熟悉的问题。但是，并不是所有的妇女都会留意自己的月经是否已经过期或月经与以往有所不同，当病人没有意识到自己已经“怀孕”而因其他躯体症状就诊于其他专科医生时，就容易被漏诊。
Abstract 1757: A 35-Year-Old Female with Anterior ST Segment Elevation and Cardiogenic Shock
Authors: Marc Bonaca, David Morrow, Carolyn Ho
Journal: Circulation (2007)

A 35 year-old female with history of spontaneous pneumothorax presented with acute onset chest pain. She was hypotensive and tachycardic. Exam revealed tall stature, distended neck veins, and diffuse crackles. CXR showed pulmonary edema, no pneuomothorax and normal cardiac and mediastinal silhouettes. Electrocardiogram showed antero-lateral ST elevation. The patient was intubated and stabilized. Transthoracic echocardiogram showed anterior wall motion abnormality, no pericardial effusion, a normal aortic root with no obvious dissection or aortic insufficiency. CT angiogram of the chest showed no aortic dissection. As no dissection was identified she was taken for cardiac catheterization for acute MI. Angiography revealed a patent right coronary and an occluded left-main. The left-main was successfully treated with angioplasty and stenting. Subsequent TEE revealed an aortic intramural hematoma adjacent to the left-main ostium. Repeat CT angiography revealed non-flow limiting dissections of the left subclavian, the superficial mesenteric, and the left internal carotid arteries. Her body habitus and presentation suggested a malignant connective tissue disorder. Family history included maternal fatal aortic rupture at age 40 and sudden death of her maternal grandfather at age 45 of unknown etiology. In addition to Marfan Syndrome, her aortic dissection without aortic dilation suggested a possible TGF-B receptor mutation (Loeys-Dietz syndrome). Genetic testing revealed a novel Fibrillin-1 mutation at intron 40. The location at the splice acceptor site of the intron/exon boundary was likely to be pathogenic. Her daughter has tall stature and normal aortic root and is undergoing mutation confirmation testing. The phenotypic characteristics of patients with Marfan and related syndromes may vary and are associated with important morbidity and mortality. Basic science and clinical translational studies have advanced our understanding of disease pathogenesis and our approach to patient care. Genetic testing offers potential for definitive identification of family members at risk. Illumination of the role of TGF-beta signaling in the pathobiology of these syndromes has led to new possibilities in treatment and diagnosis.
Abstract P147: Early Induction of Mild Hypothermia During Cardiac Arrest Enhances Neurological Benefits for Patients With Out-of-hospital Cardiac Arrest Who Underwent Extracorporeal Cardiopulmonary Resuscitation
Authors: Ken Nagao, Kimio Kikushima, Kazuhiro Watanabe, Eizo Tachibana, Yoshiteru Tominaga, Katsusige Tada, Mitsuru Ishii, Nobutaka Chiba, Asuka Kasai, Taketomo Soga, Masakazu Matuzaki, Kei Nishikawa, Yutaka Tateda, Harumi Ikeda, Tukasa Yagi
Journal: Circulation (2009)
Eye movements in spectrum personality disorders: comparison of community subjects and relatives of schizophrenic patients
Authors: G K Thaker, S Cassady, H Adami, M Moran, D E Ross
Journal: American Journal of Psychiatry (1996)

The purpose of the current study was to test the specificity of an association between eye tracking abnormality and schizophrenia spectrum personality symptoms in the family members of schizophrenic patients. The studies of biological markers for genetic vulnerability to schizophrenia, which test an association between a biological measure and schizophrenia spectrum personality symptoms, are constrained, since these personality symptoms may lack the specificity for a schizophrenic phenotype. An association between a behavioral measure and these personality symptoms in general can easily be false (i.e., not related to schizophrenic vulnerability). In contrast, a strong deviant finding in the relatives of schizophrenic patients with spectrum personality symptoms, in the presence of a relatively normal finding in spectrum subjects without a known history of schizophrenia, makes the biobehavioral measure an interesting candidate for such investigations.Seventy-five subjects recruited from the community who did not have a family history of psychosis completed the study (24 of the 75 had significant schizophrenia spectrum personality symptoms). Thirty-two first-degree relatives of schizophrenic patients (13 with spectrum symptoms) completed the study. Subjects were 18-45 years old and had no DSM-III-R axis I diagnosis.Qualitative smooth pursuit eye movement score was significantly worse in relatives with the spectrum symptoms than in spectrum subjects without a family history of schizophrenia and the nonspectrum relatives. Schizotypal and schizoid symptoms explained a significant amount of the variance in the eye tracking measure in the relatives (31% and 20%, respectively) but not in the community subjects (less than 2%). Relatives of schizophrenic patients with and without the spectrum symptoms had significantly longer antisaccade latency, in spite of comparable latency for visually guided saccades, than the community subjects.Smooth pursuit abnormality in subjects with schizophrenia spectrum personality disorders is specifically associated with a family history of schizophrenia.
Abstract 2892: Electrophysiological and Arrhythmogenic Effects of Intramyocardial Bone Marrow Cell Injection in Patients with Chronic Ischemic Heart Disease
Authors: S L Beeres, K Zeppenfeld, J J Bax, E E van der Wall, D E Atsma, M J Schalij
Journal: Circulation (2006)

Introduction Autologous bone marrow cell injection has recently been introduced to treat patients with chronic ischemic heart disease. However, inadequate incorporation of transplanted cells in the...
Major depression with mood-congruent or mood-incongruent psychotic features: outcome after 40 years
Authors: W Coryell, M T Tsuang
Journal: American Journal of Psychiatry (1985)

Using cross-sectional evaluations 40 years after index admissions, the authors compared depressed patients with mood-congruent and those with mood-incongruent psychotic features. These patients were then compared with patients with nonpsychotic major depression, schizophreniform disorder, or schizophrenia. Outcome in the mood-congruent group resembled that in the nonpsychotic group and was significantly better than that in the mood-incongruent group. Patients in this latter group, however, had significantly better follow-up scores than did schizophrenic patients. These findings are consistent with a short-term outcome and family history study and suggest that patients with major depression and mood-incongruent psychotic features constitute a more diagnostically heterogeneous group than do those with mood-congruent psychotic features.
Abstract 1718: Combination of Direct Acting FXa Inhibitor and P2Y <sub>12</sub> Antagonist at Non-Effective doses Provides Significant Inhibition of Arterial Thrombosis
Authors: Patrick Andre, Pamela B Conley, Francis Deguzman, Yvonne Pak, Mayuko Inagaki, Uma Sinha, David R Phillips
Journal: Circulation (2008)

Previous studies have shown that inhibition of FXa and P2Y 12 used individually inhibit arterial thrombosis. The present study was designed to determine the antithrombotic activity achieved by the combination of non-effective doses of PRT054021 (FXa inhibitor) and PRT060128 (P2Y 12 antagonist). Arterial thrombosis was achieved by FeCl 3 injury of mesenteric arteries of the mouse and monitored in real time using intravital microscopy. Antagonism of either FXa or P2Y 12 dose-dependently inhibited early (time for appearance of first thrombus, TFFT) and late (time to vascular occlusion, TTO) phases of thrombosis (see Table ). Maximal effects were achieved at plasma concentrations superior or equal to 1 μg/ml for the two antagonists. Interestingly, the co-administration of non-effective doses of PRT054021 and PRT060128 significantly delayed time for appearance of first thrombus and vascular occlusion, demonstrating potent synergistic antithrombotic activity. PRT054021 and PRT060128 demonstrated a strong synergistic effect when administered in combination at non-effective doses. This combination is of particular relevance in acute settings, when thrombotic risk is at its paroxysm and maximal protection is sought as early as possible. These data also indicate that combined inhibition of FXa and P2Y 12 by reversible antagonists could provide substantial benefits to ACS patients throughout the chronic phase of the disease.