tbuckley/cabot-search huggingface dataset:
ABSENCE OF BENEFICIAL EFFECTS FROM INJECTIONS OF DESOXYCORTICOSTERONE ACETATE AND OF CORTICAL ADRENAL EXTRACT IN EXPERIMENTAL ANURIA 1
Authors: Alexander W. Winkler, Paul K. Smith, Hebbel E. Hoff
Journal: Journal of Clinical Investigation (1942)

Hoff, Smith and Winkler (1) found that dogs with anuria secondary to nephrectomy or to ure- teral ligation die from cardiac arrest due to auto- intoxication with potassium.Potassium, derived from the breakdown of the animal's own tissues, can apparently neither be excreted nor stored, and gradually accumulates until a concentration suffi- cient to cause cardiac arrest is attained.A clinical state somewhat analogous to these forms of ex- perimental anuria has recently been described by Beall and others (2, 3, 4, 5) in patients with anuria of several days duration following crushing injuries.In some patients the potassium of serum rose considerably, and it seems possible that in some instances death may have been due to potassium poisoning.Since desoxycorticoste- rone acetate (hereafter called "DOCA") may, under certain circumstances, lower the serum po- tassium, the possibility that this substance might prove of therapeutic value naturally presented itself.Selye (6, 7) and Dosne (8) have in fact reported considerable prolongation of life in an- uric rats previously treated with DOCA, and have termed this effect an "antiuremic action."The present study deals mainly with the results of DOCA injections in anuric dogs.Several sup- plementary experiments with whole cortical ex- tract were carried out. MATERIALS AND METHODSThe general procedure and the specific techniques em- ployed have been described in detail previously (1).No water or food was given during the course of the experi- ments, so that vomiting with secondary chloride depletion was virtually absent.All injections of DOCA or of cortical extract were made after the ureters were ligated.
PLASTIC REPAIR OF INGUINAL HERNIA
Authors: JOSEPH A. PETTIT
Journal: JAMA (1930)

In the majority of herniorrhaphies, either direct or indirect, the chief complicating factor confronting a firm and secure closure is the necessity of making an adequate provision for the transmission of the structures of the spermatic cord. It is on this account that the closure of an inguinal hernial opening in the female is a simpler and surer procedure. The Bassini operation, though adequate in a large number of cases, is in reality no more than the removal of the enlargement of a congenital sac and resuture of the structures, plus a floor construction of muscle tissue that is not firm and the conjoined tendon that must be under unsafe tension. It presents the disadvantage of leaving the opening directly through the aponeurosis, which is the fundamental tissue support, ranking next to bone in this respect, thus leaving a postoperative "weak spot" in a vulnerable portion of the aponeurosis. With
Nonoliguric Renal Failure Associated With Zomepirac
Authors: Wesley H. Lisker
Journal: JAMA (1983)

To the Editor.—  I would like to report a case of nonoliguric acute renal failure associated with the use of zomepirac sodium.  Report of a Case.—  A 62-year-old man had no history of renal disease but had suffered three prior myocardial infarctions. After his fourth myocardial infarction, a left ventricular aneurysm developed and he was admitted to this hospital for coronary artery bypass as well as aneurysmectomy. After the operation, he suffered a left parietal stroke. His recovery from the stroke was steady, but he became depressed and agitated because of his persisting neurological deficits. He also complained of right shoulder and hip arthralgias. Consequently, a total of four 200-mg doses of zomepirac sodium were given over two days. He concomitantly received small doses of haloperidol and meprotiline. Before receiving the zomepirac sodium, his creatinine level was 1.3 mg/dL; serum urea nitrogen level, 8 mg/ dL. On the second day
ON A COURT OF MEDICAL EXPERTS IN CASES OF INSANITY
Authors: Wm. H. Stokes
Journal: American Journal of Psychiatry (1853)

INSANITY."The advantage and exodiency of establishing by law, in each State or district, a board of commissioners 01 experts, for the purpose of in #{231}cstigating and tesz fying in trials, criminal and civil, where the questions of mental soundness areinvolved."
Etude comparative des différents types de dissecteurs à injection d'eau avec ESD calibrée chez 25 porcs
Authors: JC Letard, F Cessot, JM Canard, PA Dalbiès, JP Carle, B Kieffer, P Capot, RP Charles, D Sautereau
Journal: Endoscopy (2010)

Introduction: L'ESD s'effectue avec des dissecteurs simples à courant haute fréquence ou avec des dissecteurs à injection d'eau sous pression. Le but de ce travail était d'apprécier l'efficacité et l'innocuité des deux types de dissecteurs à eaux: Flush Knife et Erbe Jet.
Clinical and Genetic Heterogeneity of Latent Autoimmune Diabetes in Adults
Authors: Michiaki Fukui, Yoshihiro Kitagawa, Naoto Nakamura, Toshikazu Yoshikawa
Journal: Diabetes Care (2003)

We read with great interest the recent article by Hosszufalusi et al. (1) reporting that latent autoimmune diabetes in adults (LADA) manifests clinical features similar to those of adult-onset type 1 diabetes with rapid progression, and that prevalences of predisposing alleles and haplotypes did not differ between these two forms of autoimmune diabetes. Patients with LADA have been found to be heterogeneous in their clinical attributes (2). Some patients develop insulin deficiency within a few years (LADA-type 1), while others show clinical and metabolic markers similar to patterns in antibody-negative type 2 diabetes (LADA-type 2). As the authors noted, selection …
Beyond insulin resistance: Innate immunity in nonalcoholic steatohepatitis
Authors: Jacquelyn J. Maher, Pablo Leon, James C. Ryan
Journal: Hepatology (2008)

Obesity is an inflammatory disorder characterized by heightened activity of the innate immune system. Innate immune activation is central to the development of obesity-related insulin resistance; it also plays an important role in obesity-related tissue damage, such as that seen in atherosclerosis. Recent research has implicated the innate immune system in the pathophysiology of obesity-related liver disease. This review summarizes how innate immune processes, occurring both within and outside the liver, cause not only insulin resistance but also end-organ damage in the form of nonalcoholic fatty liver disease.
Increased incidence of inflammatory bowel disease in Québec residents with airway diseases
Authors: Paul Brassard, Maria Vutcovici, Pierre Ernst, Valérie Patenaude, Maida Sewitch, Samy Suissa, Alain Bitton
Journal: European Respiratory Journal (2014)

The objective of the study was to assess whether the incidences of Crohn’s disease and ulcerative colitis are increased in patients with asthma and chronic obstructive pulmonary disease (COPD) compared to the general population. A population-based retrospective cohort study was conducted using the administrative health databases of Québec, Canada. Incidences of Crohn’s disease and ulcerative colitis among patients with asthma and COPD were assessed for the 2001–2006 period. In total, 136 178 subjects with asthma and 143 904 subjects with COPD were identified. The average incidence of Crohn’s disease and ulcerative colitis was 23.1 and 8.8 per 100 000 person-years among asthmatic patients; in the COPD cohort there were 26.2 Crohn’s disease cases and 17 ulcerative colitis cases per 100 000 person-years. The incidence of Crohn’s disease in asthma and COPD patients was 27% and 55% higher than in the general population of Québec; the incidence of ulcerative colitis was 30% higher among COPD patients compared to the general population. Incidence of inflammatory bowel disease was significantly increased in asthma and COPD patients compared to the general population of Québec. Incidence rates were particularly high in patients with COPD. Awareness of an association between airway diseases and inflammatory bowel disease in older age groups may play an important role in earlier detection of bowel disease and in the therapeutic management of such patients.
Propafenone During Acute Myocardial Ischemia in Patients: A Double-Blind, Randomized, Placebo-Controlled Study
Authors: Thomas S Faber, Manfred Zehender, Olaf Krahnefeld, Karin Daisenberger, Thomas Meinertz, Hanjörg Just
Journal: Journal of the American College of Cardiology (1997)
Expression and sequence analyses of p33<sup><i>ING1</i></sup> gene in myeloid leukemia
Authors: K. Ito, K. Kinjo, T. Nakazato, Y. Ikeda, M. Kizaki
Journal: American Journal of Hematology (2002)

p33(ING1) is a novel candidate tumor suppressor gene which is involved in the regulation of apoptosis. p33(ING1) interacts with p53 signaling pathway and regulates cellular growth. It has reported that the expression of p33(ING1) mRNA was decreased in lymphoid malignancies. We thus investigated the potential involvement of p33(ING1) abnormalities in myeloid leukemias. However, the levels of p33(ING1) transcript were almost equal in 3 AML cell lines and 10 fresh AML samples. In addition, neither point mutations nor deletions in p33(ING1) gene were found in myeloid leukemias. These results suggest that p33(ING1) may not be a major candidate tumor suppressor gene in myeloid leukemias.
Abstract 5650: Targeting siRNA to tumors and their stroma as a dual anticancer and anti-angiogenic therapy
Authors: Paula Ofek, Wiebke Fischer, Marcelo Calderon, Rainer Haag, Ronit Satchi-Fainaro
Journal: Cancer Research (2012)

Abstract New targets for RNA interference (RNAi)-based cancer therapy are constantly emerging from the increasing knowledge on the molecular pathways involved in carcinogenesis. Nevertheless, in vivo delivery of small interfering RNA (siRNA) remains a crucial challenge for its therapeutic success. SiRNAs on their own are not taken-up by most mammalian cells in a way that preserves their activity. In order to circumvent these limitations, we developed a cationic carrier system, which can strongly improve its stability, intracellular trafficking and silencing efficacy. We have recently developed a polyglycerol (PG)-Amine, a water-soluble polyglycerol-based dendrimer that accumulates in the tumor environment due to the enhanced permeability and retention (EPR) effect, and therefore, represents an ideal delivery vehicle for antitumor biological agents. PG-Amine entrapment of siRNA neutralized its negative charge in a dose-dependent manner and significantly improved its cellular uptake. The luciferase gene, ectopically overexpressed in U87 human glioblastoma cell line was used as a model system and its silencing efficacy was extensively evaluated both in vitro and in vivo. Following encouraging results obtained from several cancer cell lines, the silencing efficiency of the nanocarrier luciferase-siRNA polyplexes was followed-up in vivo by non-invasive intravital bioluminescence imaging. A significant gene silencing effect was accomplished in vivo in both human glioblastoma and murine mammary adenocarcinoma mouse models following intravenous administration of our polyplexes. We further characterized the effect of silencing a few selected key proteins (e.g. Notch1) in vitro and achieved significant effects on the proliferation and migration of glioblastoma and neuroblastoma cell lines. In conclusion, we predict that specific delivery of siRNA to tumor epithelial and endothelial cells in vivo, and silencing of an important cell growth and angiogenesis regulator will warrant this approach as a successful anticancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5650. doi:1538-7445.AM2012-5650
Varieties of uncertainty monitoring
Authors: John H. Flavell
Journal: Behavioral and Brain Sciences (2003)

Three types or levels of uncertainty monitoring are distinguished: (1) uncertainty responding but no feelings of uncertainty, (2) conscious feelings of uncertainty, (3) conscious feelings of uncertainty plus reflective awareness of what these feelings are and mean. It is hypothesized that only the first and perhaps the second occur in animals and human infants, whereas all three occur in older humans. Two possible lines of future research are also suggested.
Excessive Mood Elevation and Behavioral Activation with Antidepressant Treatment of Juvenile Depressive and Anxiety Disorders: A Systematic Review
Authors: Emanuela Offidani, Giovanni A. Fava, Elena Tomba, Ross J. Baldessarini
Journal: Psychotherapy and Psychosomatics (2013)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The prevalence, characteristics and implications of excessive arousal-activation in children and adolescents treated with antidepressants for specific illnesses have not been systematically examined. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We compared reports of antidepressant trials (n = 6,767 subjects) in juvenile depressive (n = 17) and anxiety disorders (n = 25) for consensus-based indications of psychopathological mood elevation or behavioral activation. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Rates of excessive arousal-activation during treatment with antidepressants were at least as high in juvenile anxiety (13.8%) as depressive (9.79%) disorders, and much lower with placebos (5.22 vs. 1.10%, respectively; both p &lt; 0.0001). The antidepressant/placebo risk ratio for such reactions in paired comparisons was 3.50 (12.9/3.69%), and the meta-analytically pooled rate ratio was 1.7 (95% confidence interval: 1.2-2.2; both p ≤ 0.001). Overall rates for ‘mania or hypomania', specifically, were 8.19% with and 0.17% without antidepressant treatment, with large drug/placebo risk ratios among depressive (10.4/0.45%) and anxiety (1.98/0.00%) disorder patients. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Risks of excessive mood elevation during antidepressant treatment, including mania-hypomania, were much greater than with placebo, and similar in juvenile anxiety and depressive disorders. Excessive arousal-activation in children or adolescents treated with antidepressants for anxiety as well as depressive disorders calls for particular caution and monitoring for potential risk of future bipolar disorder.
Metal composition of ambient PM2.5 influences severity of allergic airways disease in mice.
Authors: Stephen H Gavett, Najwa Haykal-Coates, Lisa B Copeland, Joachim Heinrich, M Ian Gilmour
Journal: Environmental Health Perspectives (2003)

Children living in Hettstedt in eastern Germany have been reported to have a higher prevalence of sensitization to common aeroallergens than another cohort living in the neighboring city of Zerbst; these differences correlated with the presence of industrial air pollution. Samples of fine particulate matter (< 2.5 micro m aerodynamic diameter; PM(2.5)) collected in Hettstedt in 1999 had several-fold higher levels of zinc, magnesium, lead, copper, and cadmium than samples from Zerbst. To determine if the results from epidemiologic studies could be repeated in an animal model, we administered PM(2.5) from Hettstedt and Zerbst to ovalbumin-allergic mice. In Balb/c mice, PM(2.5) from Hettstedt, but not PM(2.5) from Zerbst or control filter extract, caused a significant increase in immediate responses to ovalbumin challenge when aspirated 2 hr before challenge, but not when aspirated immediately before sensitization 2 weeks earlier. Antigen-specific IgE was increased by Hettstedt PM(2.5) whether administered before sensitization or challenge. Airway responsiveness to methacholine aerosol and lung inflammatory cell numbers were significantly increased only in allergic mice exposed to Hettstedt PM(2.5) before challenge. Both Hettstedt and Zerbst PM(2.5) significantly increased lung injury parameters and proinflammatory cytokines. These results are consistent with epidemiologic findings and show that metal composition of ambient PM(2.5) influences the severity of allergic respiratory disease.
E6AP ubiquitin ligase regulates PML-induced senescence in Myc-driven lymphomagenesis
Authors: Kamil Wolyniec, Jake Shortt, Elisa de Stanchina, Yaara Levav-Cohen, Osnat Alsheich-Bartok, Igal Louria-Hayon, Vincent Corneille, Beena Kumar, Simone J. Woods, Stephen Opat, Ricky W. Johnstone, Clare L. Scott, David Segal, Pier Paolo Pandolfi, Stephen Fox, Andreas Strasser, Yong-Hui Jiang, Scott W. Lowe, Sue Haupt, Ygal Haupt
Journal: Blood (2012)
The Calcium Sensitizer Levosimendan Improves Human Diaphragm Function
Authors: Jonne Doorduin, Christer A. Sinderby, Jennifer Beck, Dick F. Stegeman, Hieronymus W. H. van Hees, Johannes G. van der Hoeven, Leo M. A. Heunks
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Acquired diaphragm muscle weakness is a key feature in several chronic conditions, including chronic obstructive pulmonary disease, congestive heart failure, and difficult weaning from mechanical ventilation. No drugs are available to improve respiratory muscle function in these patients. Recently, we have shown that the calcium sensitizer levosimendan enhances the force-generating capacity of isolated diaphragm fibers.Objectives: To investigate the effects of the calcium sensitizer levosimendan on in vivo human diaphragm function.Methods: In a double-blind, randomized, crossover design, 30 healthy subjects performed two identical inspiratory loading tasks. After the first loading task, subjects received levosimendan (40 μg/kg bolus followed by 0.1/0.2 μg/kg/min continuous infusion) or placebo. Transdiaphragmatic pressure, diaphragm electrical activity, and their relationship (neuromechanical efficiency) were measured during loading. Magnetic phrenic nerve stimulation was performed before the first loading task and after bolus administration to assess twitch contractility. Center frequency of diaphragm electrical activity was evaluated to study the effects of levosimendan on muscle fiber conduction velocity.Measurements and Main Results: The placebo group showed a 9% (P = 0.01) loss of twitch contractility after loaded breathing, whereas no loss in contractility was observed in the levosimendan group. Neuro-mechanical efficiency of the diaphragm during loading improved by 21% (P < 0.05) in the levosimendan group. Baseline center frequency of diaphragm electrical activity was reduced after levosimendan administration (P < 0.05).Conclusions: The calcium sensitizer levosimendan improves neuromechanical efficiency and contractile function of the human diaphragm. Our findings suggest a new therapeutic approach to improve respiratory muscle function in patients with respiratory failure.
IL-6 and Ovarian Cancer—Letter
Authors: Jason W. Locasale, Benjamin Zeskind
Journal: Clinical Cancer Research (2011)

Clinical Cancer Research recently published an important study by Coward and colleagues (1) examining interleukin-6 as a target in ovarian cancer and last year published an investigation of the same target in prostate cancer by Dorff and colleagues (2). Examining these two studies together may yield additional insights.In the 4 of 18 patients with ovarian cancer who had stable disease for 6 months or more, the plasma concentration of VEGF declined significantly during treatment. This raises the possibility that the mechanism of action of siltuximab may involve the reduction of VEGF levels.Dorff and colleagues examined a cohort of 53 patients with castration-resistant prostate cancer, finding that overall survival following siltuximab treatment was significantly better in patients with higher baseline levels of soluble epidermal growth factor receptor (sEGFR) than those with lower levels.What is the relationship between these two findings? It is well established that IL-6 signaling can upregulate hypoxia-inducible factor-1 (HIF-1) via STAT3 (3) and that HIF-1 in turn promotes VEGF expression. EGFR signaling can also promote VEGF expression through both HIF-1–dependent and HIF-1–independent mechanisms (4).We hypothesize that the effect of siltuximab on VEGF may depend on the level of EGFR signaling present. In patients with low levels of EGFR signaling (as may be indicated by high levels of sEGFR), siltuximab alone should be sufficient to reduce VEGF production. However, in patients with high levels of EGFR signaling, a combination of siltuximab and an agent targeting the EGFR pathway may be necessary.This hypothesis is supported by the recent findings of Song and colleagues that the combination of siltuximab with an EGFR inhibitor was significantly more effective than either therapy alone in reducing tumor volume in mice bearing non–small cell lung cancer (NSCLC) xenografts (5).Coward and colleagues articulate the need to identify subgroups of patients most likely to respond to siltuximab. Examining baseline levels of sEGFR, and other markers of EGFR signaling, is one possible approach. If subsequent studies confirm that siltuximab is more efficacious in patients with lower EGFR signaling, it would suggest that patients with higher EGFR signaling could derive increased benefit from the combination of siltuximab and agents targeting EGFR.See the Response, p. 7838J.W. Locasale and B. Zeskind are employees of Immuneering Corporation and B. Zeskind has ownership interest in Immuneering Corporation.
Two Steps Forward in the Treatment of Colorectal Cancer
Authors: Robert J. Mayer
Journal: New England Journal of Medicine (2004)

Until recently, fluorouracil was the only effective systemic treatment for colorectal cancer. It acts primarily by inhibiting thymidylate synthase, a key enzyme in DNA synthesis, and because leucovorin (folinic acid) enhances this effect, fluorouracil and leucovorin (FL) are given together. FL has been given in various dose schedules, with a continuous infusion appearing slightly more effective than a bolus.1 FL reduces tumor size by 50 percent or more (objective response) in approximately 20 percent of patients with advanced colorectal cancer and prolongs median survival from approximately 6 months (without treatment) to about 11 months.2 When given as adjuvant therapy after . . .
Initial poor quality of life and new onset of dyspepsia: results from a longitudinal 10-year follow-up study
Authors: A. C Ford, D. Forman, A. G Bailey, A. T R Axon, P. Moayyedi
Journal: Gut (2006)

<b>Background:</b> Numerous studies examining the prevalence and natural history of dyspepsia in the general population have been conducted. However, few have reported the effect of quality of life on the development of dyspepsia. A 10-year longitudinal follow-up study examining the effect of quality of life on subsequent dyspepsia was performed. <b>Methods:</b> Individuals originally enrolled in a population-screening programme for <i>Helicobacter pylori</i> were contacted through a validated postal dyspepsia questionnaire. Baseline demographic data, quality of life at original study entry, and dyspepsia and irritable bowel syndrome (IBS) symptom data were already on file. Consent to examine primary-care records was sought, and data regarding non-steroidal anti-inflammatory drugs (NSAID) and aspirin use were obtained from these. <b>Results:</b> Of 8407 individuals originally involved, 3912 (46.5%) provided symptom data at baseline and 10-year follow-up. Of 2550 (65%) individuals asymptomatic at study entry, 717 (28%) developed new-onset dyspepsia at 10 years, an incidence of 2.8% per year. After multivariate logistic regression, lower quality of life at study entry (OR 2.63; 99% CI 1.86 to 3.71), higher body mass index (OR per unit 1.05; 99% CI 1.02 to 1.08), presence of IBS at study entry (OR 3.1; 99% CI 1.51 to 6.37) and use of NSAIDs and/or aspirin (OR 1.32; 99% CI 0.99 to 1.75) were significant risk factors for new-onset dyspepsia. <b>Conclusions:</b> The incidence of new-onset dyspepsia was almost 3% per year. Low quality of life at baseline exerted a strong effect on the likelihood of developing dyspepsia at 10 years.