tbuckley/cabot-search huggingface dataset:
T. E. Lawrence: A Study of Heroism and Conflict
Authors: JOHN E. MACK
Journal: American Journal of Psychiatry (1969)

There is a great need to deepen our understanding of the psychological forces which motivate individuals whose actions in the public sphere affect the lives of all of us. T. E. Lawrence, because of an extraordinary gift of psychological insight and a compelling need for introspection brought about by his emotional suffering in World War I, has proved to be an excellent subject for such study. In this essay the author concentrates on one aspect of his psychology, the problem of self-esteem, and the relationship between this problem and Lawrence's public actions.
<i>N</i>-Methyl-<scp>d</scp>-Aspartic Acid Receptor Expression in the Dorsolateral Prefrontal Cortex of Elderly Patients With Schizophrenia
Authors: Stella Dracheva, Salvatore A.E. Marras, Sharif L. Elhakem, Fred R. Kramer, Kenneth L. Davis, Vahram Haroutunian
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The N-methyl-d-aspartic acid (NMDA) class of glutamate receptors has received attention in the pathophysiology of schizophrenia because of the similarity between some schizophrenic symptoms and symptoms caused by NMDA antagonists. To determine if NMDA receptor abnormalities were present at the mRNA level, expression of NMDA receptor (NR) subunits NR1, NR2A, and NR2B was measured in specimens from the dorsolateral prefrontal cortex and the occipital cortex of elderly patients with schizophrenia and normal elderly subjects. METHOD: Postmortem specimens from antemortem assessed and diagnosed elderly patients with schizophrenia (N=26) were compared with those from a neuropathologically and neuropsychiatrically normal elderly comparison group (N=13) and from patients with Alzheimer's disease (N=10). The mRNA expression of the NR1, NR2A, and NR2B subunits and of postsynaptic density 95 (PSD-95), a protein associated with postsynaptic NMDA receptors, was studied with quantitative real-time reverse transcriptase polymerase chain reaction. RESULTS: Expression of NR1 and NR2A but not NR2B subunits was higher in the dorsolateral prefrontal cortex and the occipital cortex of patients with schizophrenia than in the normal and Alzheimer's disease groups. In contrast, NR1 expression was significantly lower in the Alzheimer's disease group. Occipital cortex expression of PSD-95 was higher in the schizophrenic subjects and correlated strongly with the expression of NR2A and NR2B in both cortical regions and with expression of NR1 in the occipital cortex. These results were not influenced by neuroleptic exposure history, postmortem interval, or age of the subject. CONCLUSIONS: NMDA receptor subunits are abnormally expressed in elderly patients with schizophrenia. The disproportionate expression of the NR1 and NR2A subunits relative to NR2B expression may have implications for the pathophysiology of schizophrenia and the sensitivity of schizophrenic patients to glutamate and glutamatergic drugs.
Absence of human parvovirus B19 DNA in myoepithelial sialadenitis of primary Sjogren's syndrome
Authors: V De Re
Journal: Annals of the Rheumatic Diseases (2002)

<h3>ABSTRACT</h3> Hypertrophic Cardiomyopathy (HCM) is a pathological condition characterized by an abnormal thickening of the myocardium. When it affects the medio-basal portion of the septum, it is named Hypertrophic Obstructive Cardiomyopathy because it induces a flow obstruction in the left ventricle outflow tract, which may compromise the cardiac function and possibly lead to cardiac death. In this work, we investigate the hemodynamics of different HCM patients by means of computational hemodynamics, aiming at quantifying the effects of this pathology on blood flow and pressure gradients and thus providing clinical indications that may help diagnosis and the design of surgical treatment (septal myectomy). To this aim, we employ an enhanced version of an image-based computational pipeline proposed in a previous work, integrating fluid dynamics simulations with geometrical and functional data reconstructed from standard cine-MRI acquisitions. Blood flow is modelled as an incompressible Newtonian fluid, The corresponding Navier-Stokes equations are solved in a moving domain obtained from cine-MRI, whereas the valve leaflets are accounted for by a resistive method.
In Vivo Insulin Sensitivity and Secretion in Obese Youth
Authors: Fida Bacha, Neslihan Gungor, SoJung Lee, Silva A. Arslanian
Journal: Diabetes Care (2008)

Impaired glucose tolerance (IGT) represents a pre-diabetic state. Controversy continues in regards to its pathophysiology. The aim of this study was to investigate the differences in insulin sensitivity (IS) and secretion in obese adolescents with IGT compared with those with normal glucose tolerance (NGT) and type 2 diabetes.
Cysteinyl leukotriene overproduction in aspirin-exacerbated respiratory disease is driven by platelet-adherent leukocytes
Authors: Tanya M. Laidlaw, Molly S. Kidder, Neil Bhattacharyya, Wei Xing, Shiliang Shen, Ginger L. Milne, Mariana C. Castells, Heng Chhay, Joshua A. Boyce
Journal: Blood (2012)
Six doctors are charged with taking kickbacks for sending patients to Chicago hospital for no reason
Authors: O. Dyer
Journal: BMJ (2015)

An entire Chicago hospital operated on kickbacks, buying referrals of elderly patients who had no medical reason for admission, then billing Medicare and Medicaid for unneeded investigations and stays, say charges filed by US attorneys against five administrators and six doctors. 

Conditions at Sacred Heart Hospital, in a deprived area of the city’s West Side, were so poor that the hospital “was required to purchase patients” from unscrupulous local doctors, disguising payments as office rent or teaching fees, the prosecutors allege. 

By the time the hospital was raided in April 2013, conversations among senior staff were being routinely recorded for the FBI by a doctor and administrators who hoped to secure lenient treatment for their own acts. The hospital’s deputy chief executive officer and vice president, both cooperating sources for the FBI, recently entered guilty pleas in preliminary hearings. Prosecutors are expected to ask for lesser sentences of two and five years in prison in return for their cooperation.

But the evidence recorded did not permit the government to press charges on the gravest allegations made in the criminal complaint filed soon after the initial arrests: that doctors at the hospital deliberately suppressed patients’ respiration with heavy sedation so that they could perform lucrative tracheotomies that often ended in the patient’s death.1

The trial begins this month, and key details of the government’s case have just become public. Prominent among the defendants are the hospital’s chief executive officer, Edward Novak, 59, and Venkateswara Kuchipudi, 67, whom staff referred to as Chicago’s “king of nursing homes.” He had patients taken to Sacred Heart from his facilities …
Evidence-Based and Potential Benefits of Metformin in the Polycystic Ovary Syndrome: A Comprehensive Review
Authors: Stefano Palomba, Angela Falbo, Fulvio Zullo, Francesco Orio
Journal: Endocrine Reviews (2008)

Metformin is an insulin sensitizer widely used for the treatment of patients affected by type 2 diabetes mellitus. Because many women with polycystic ovary syndrome (PCOS) are insulin resistant, metformin was introduced in clinical practice to treat these patients also. Moreover, metformin's effect has other targets beside its insulin-sensitizing action. The present review was aimed at describing all evidence-based and potential uses of metformin in PCOS patients. In particular, we will analyze the uses of metformin not only for the treatment of all PCOS-related disturbances such as menstrual disorders, anovulatory infertility, increased abortion, or complicated pregnancy risk, hyperandrogenism, endometrial, metabolic and cardiovascular abnormalities, but also for the prevention of the syndrome.
Immunohistochemical Detection of Human Basophils in Postmortem Cases of Fatal Asthma
Authors: CHRISTOPHER L. KEPLEY, PATRICIA J. McFEELEY, JANET M. OLIVER, MARY F. LIPSCOMB
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The role of human basophils in bronchial asthma has been hard to define. In this study, we used the basophil-specific monoclonal antibody (mAb), 2D7, in postmortem lung sections from individuals who die in status asthmaticus (fatal asthma [FA]) to determine if the pathology of FA is associated with an increase in basophil numbers in the lung. As controls, we used lung sections of patients who had a history of asthma but died from nonasthmatic causes (nonfatal asthma [NFA]) as well as patients with no history of asthma (control [C]). In lung sections from all three groups, basophils were scattered throughout the large and small airways, airway epithelium, submucosa, and alveolar walls. The numbers of basophils in the lungs of patients with FA ranged from 41 to 119 cells/mm2, significantly more than the numbers of basophils in lungs from individuals with a history of asthma (NFA; 0 to 16 cells/ mm2) and in the control lungs (C; 0 to 13 cells/mm2). In contrast, CD45-positive cells were not significantly different in the airways of FA and NFA, although there were significant increases in the two groups compared with control subjects. In summary, basophil infiltration was significantly increased in lungs from individuals who died from asthma, supporting the hypothesis that basophils are involved in the pathogenesis of FA.
Targeted depletion of lymphotoxin-α–expressing TH1 and TH17 cells inhibits autoimmune disease
Authors: Eugene Y Chiang, Ganesh A Kolumam, Xin Yu, Michelle Francesco, Sinisa Ivelja, Ivan Peng, Peter Gribling, Jean Shu, Wyne P Lee, Canio J Refino, Mercedesz Balazs, Andres Paler-Martinez, Allen Nguyen, Judy Young, Kai H Barck, Richard A D Carano, Ron Ferrando, Lauri Diehl, Devavani Chatterjea, Jane L Grogan
Journal: Nature Medicine (2009)
Gene therapy for arterial thrombosis
Authors: G Vassalli
Journal: Cardiovascular Research (1997)

Conventional antithrombotic treatments with antiplatelet, anticoagulant or fibrinolytic drugs are not uniformly successful and are associated with hemorrhagic side effects. Thus, new approaches to the prevention and treatment of arterial thrombosis are desirable. The gene transfer approach is particularly attractive because of its unique ability to express an antithrombotic gene at selected sites of the vessel wall (where thrombosis is threatened) while avoiding systemic anticoagulation. Clinical conditions potentially amenable to antithrombotic gene therapy include coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, peripheral artery angioplasty or thrombectomy, intravascular stenting, and vascular graft prostheses. Gene therapy may prove effective in preventing subacute thrombosis in these settings and, eventually, may play an adjuvant role to systemic thrombolysis in the treatment of acute arterial occlusion. The introduction of an antithrombotic gene into the arterial wall can be achieved either by direct in vivo gene transfer (e.g., by luminal administration of a viral vector) or by in vitro genetic manipulation of cells before their seeding onto vascular grafts, stents, or denuded arteries. The direct gene transfer approach has been used to deliver antithrombotic genes to animal arteries in vivo. Antithrombotic genes used to date include those encoding enzymes of the prostacyclin synthetic pathway, nitric oxide synthase, the thrombin inhibitor hirudin, and thrombomodulin. The in vitro gene transfer approach has been used to enhance the fibrinolytic activity of vascular grafts by overexpressing plasminogen activators. If the initial successes of gene therapy for thrombotic disease in animal models are confirmed by longer-term experiments, and if new vectors are developed which permit prolonged transgene expression without inflammation, human studies can be initiated.
Critical role of CNS effects of aldosterone in cardiac remodeling post-myocardial infarction in rats
Authors: A LAL, J VEINOT, F LEENEN
Journal: Cardiovascular Research (2004)

Oral administration of spironolactone improves cardiac remodeling and its central infusion prevents the increase in sympathetic drive post-myocardial infarction (MI). We hypothesized that central actions of aldosterone contribute to cardiac remodeling post-MI.To compare the effects of intracerebroventricular (icv) infusion and oral administration of spironolactone on cardiac remodeling and left ventricle (LV) dysfunction post-MI in rats.Spironolactone was administered orally (80 mg/kg/day) or by icv infusion (100 ng/h), starting 1-3 days post-MI in Wistar rats and continued for 6 weeks.At 6 weeks post-MI, in the rats treated with vehicle, LV peak systolic pressure (LVPSP) and LV dP/dt max were clearly decreased and LV end diastolic pressure (LVEDP) and plasma catecholamines and serum aldosterone increased. All these parameters improved with both oral and icv spironolactone. The MI-induced increases in internal circumferences of LV and right ventricle (RV), and in interstitial and perivascular fibrosis, in both the LV and RV were significantly prevented/inhibited by both oral and icv spironolactone. Laminin, fibronectin and fibrillar collagen (visualized by scanning electron microscopy, SEM) increased in the non-infarcted part of the LV post-MI in the vehicle group, but not/less in rats on oral or icv spironolactone.Since the magnitude of beneficial effects of icv spironolactone at low doses was largely equal to that achieved with its oral administration at much higher doses, we propose that in addition to other sites of action, aldosterone appears to activate central nervous system (CNS) pathways and thereby influences peripheral mechanisms involved in cardiac remodeling.
Pregnancy Outcome Following Gestational Exposure to Venlafaxine: A Multicenter Prospective Controlled Study
Authors: Adrienne Einarson, Bumn Fatoye, Moumita Sarkar, Sharon Voyer Lavigne, Joanne Brochu, Christina Chambers, Pierpaolo Mastroiacovo, Antonio Addis, Doreen Matsui, Lavinia Schuler, Thomas R. Einarson, Gideon Koren
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Because there are no studies available on the safety of venlafaxine during pregnancy, the authors' goal in this study was to determine whether venlafaxine increases the risk for major malformations. METHOD: Data on 150 women exposed to venlafaxine during pregnancy in seven pregnancy counseling centers were compared with data from studies of pregnant women who 1) received selective serotonin reuptake inhibitor antidepressants (SSRIs) (N=150) and 2) who received nonteratogenic drugs (N=150). RESULTS: Among the 150 women who were exposed to venlafaxine during pregnancy, 125 had live births, 18 had spontaneous abortions, and seven had therapeutic abortions; two of the babies had major malformations. There were no significant differences between these women and the two comparison groups on any of the measures analyzed. CONCLUSIONS: These results suggest that the use of venlafaxine during pregnancy does not increase the rates of major malformations above the baseline rate of 1%–3%.
A Photon Counting Technique for Quantitatively Evaluating Progression of Peritoneal Tumor Dissemination
Authors: Kazuyoshi Yanagihara, Misato Takigahira, Fumitaka Takeshita, Teruo Komatsu, Kazuto Nishio, Fumio Hasegawa, Takahiro Ochiya
Journal: Cancer Research (2006)

We recently established a mouse model of peritoneal dissemination of human gastric carcinoma, including the formation of ascites, by orthotopic transplantation of cultured gastric carcinoma cells. To clarify the processes of expansion of the tumors in this model, nude mice were sacrificed and autopsied at different points of time after the orthotopic transplantation of the cancer cells for macroscopic and histopathologic examination of the tumors. The cancer cells grew actively in the gastric submucosa and invaded the deeper layers to reach the serosal plane. The tumor cells then underwent exfoliation and became free followed by the formation of metastatic lesions initially in the greater omentum and subsequent colonization and proliferation of the tumors on the peritoneum. Although this model allowed the detection of even minute metastases, it was not satisfactory from the viewpoint of quantitative and objective evaluation. To resolve these problems, we introduced a luciferase gene into this tumor cell line with a high metastasizing potential and carried out in vivo photon counting analysis. This photon counting technique was found to allow objective and quantitative evaluation of the progression of peritoneal dissemination on a real-time basis. This animal metastatic model is useful for monitoring the responses of tumors to anticancer agents.
Multimodal Fetal Transesophageal Echocardiography for Fetal Cardiac Intervention in Sheep
Authors: Thomas Kohl, Martin Westphal, Danja Strümper, Sarah Achenbach, Susan Halimeh, Philipp Petry, Sebastian Aryee, Tim Buller, Rasa Aleksiene, Boulos Asfour, Ralf Witteler, Johannes Vogt, Hugo Van Aken, Hans H. Scheld
Journal: Circulation (2001)

Background The overall performance of available mechanical intravascular ultrasound catheters for fetal transesophageal echocardiography during fetoscopic fetal cardiac interventions in sheep has been limited by radioelectronic interference, low system frame rates, and low acoustic outputs. Therefore, a more reliable device is desired for human fetoscopic surgical procedures. Methods and Results We assessed the potential of a newly available 10-French phased-array intravascular ultrasound catheter for multimodal fetal transesophageal echocardiography in 5 fetal sheep between 78 and 98 days of gestation (term, 145 to 150 d). The intravascular ultrasound catheter was easily inserted through the mouth into the esophagus in all 5 sheep fetuses (mean weight, 600 g), and it permitted high-quality 2D imaging of the fetal heart in vertical imaging planes that were validated by MRI. Color Doppler and pulsed Doppler imaging permitted clear assessment of fetal cardiovascular flows and recording of velocity-time integral tracings of the fetal heart and great vessels. The vertical imaging planes were particularly useful to demonstrate interventional material inside the fetal heart and great vessels. Conclusions Our early experience with the phased-array intravascular ultrasound catheter indicates that multimodal fetal transesophageal echocardiography has now become possible in these smallest of patients.
P0108 : Overexpression of the genetic effector pathway of inflammasome in Peripheral Blood Mononucleated Cells (PBMC) of patients with acute on chronic liver failure
Authors: E. Gola, A. Brocca, S. Piano, A. Sticca, F. Morando, S. Rosi, M. Cavallin, M. Stanco, A. Romano, S. Fasolato, P. Angeli
Journal: Journal of Hepatology (2015)
Familial Aggregation of Illness Chronicity in Recurrent, Early-Onset Major Depression Pedigrees
Authors: Francis M Mondimore, Peter P Zandi, Dean F Mackinnon, Melvin G McInnis, Erin B Miller, Raymond P Crowe, William A Scheftner, Diana H Marta, Myrna M Weissman, Douglas F Levinson, Kathleen P Murphy-Ebenez, J Raymond Depaulo, James B Potash
Journal: American Journal of Psychiatry (2006)

Objective: The authors used a large sample collected for genetic studies to determine whether a chronic course of illness defines a familial clinical subtype in major depressive disorder. Method: A measure of lifetime chronicity of depressive symptoms (substantial mood symptoms most or all of the time) was tested for familial aggregation in 638 pedigrees from the Genetics of Recurrent Early-Onset Depression (GenRED) project. Results: In subjects with chronic depression, the mean age at illness onset was lower and rates of attempted suicide, panic disorder, and substance abuse were higher than among those with nonchronic depression. Chronicity was assessed in 37.8% of affected first-degree relatives of probands with chronic depression and in 20.2% of relatives of probands with nonchronic depression. Analysis using the generalized estimating equation model yielded an odds ratio of 2.52 (SE=0.39, z=6.02, p<0.0001) for the likelihood of chronicity in a proband predicting chronicity in an affected relative. With stratification by proband age at illness onset, the odds ratio for chronicity in relatives by proband chronicity status was 6.17 (SE=2.09, z=5.35, p<0.0001) in families of probands whose illness onset was before age 13 and 1.92 (SE=0.34, z=3.72, p<0.0001) in families of probands whose illness started at age 13 or later. Conclusions: These findings suggest that chronicity of depressive symptoms is familial, especially in preadolescent-onset illness. Chronicity is also associated with other indicators of illness severity in recurrent, early-onset major depression. Further study using chronicity as a subtype in the genetic analysis of depressive illness is warranted. Refinement of the definition of chronicity in depressive illness may increase the power of such studies.
Aurora Kinases as Anticancer Drug Targets
Authors: Oliver Gautschi, Jim Heighway, Philip C. Mack, Phillip R. Purnell, Primo N. Lara, David R. Gandara
Journal: Clinical Cancer Research (2008)

Abstract The human aurora family of serine-threonine kinases comprises three members, which act in concert with many other proteins to control chromosome assembly and segregation during mitosis. Aurora dysfunction can cause aneuploidy, mitotic arrest, and cell death. Aurora kinases are strongly expressed in a broad range of cancer types. Aurora A expression in tumors is often associated with gene amplification, genetic instability, poor histologic differentiation, and poor prognosis. Aurora B is frequently expressed at high levels in a variety of tumors, often coincidently with aurora A, and expression level has also been associated with increased genetic instability and clinical outcome. Further, aurora kinase gene polymorphisms are associated with increased risk or early onset of cancer. The expression of aurora C in cancer is less well studied. In recent years, several small-molecule aurora kinase inhibitors have been developed that exhibit preclinical activity against a wide range of solid tumors. Preliminary clinical data from phase I trials have largely been consistent with cytostatic effects, with disease stabilization as the best response achieved in solid tumors. Objective responses have been noted in leukemia patients, although this might conceivably be due to inhibition of the Abl kinase. Current challenges include the optimization of drug administration, the identification of potential biomarkers of tumor sensitivity, and combination studies with cytotoxic drugs. Here, we summarize the most recent preclinical and clinical data and discuss new directions in the development of aurora kinase inhibitors as antineoplastic agents.