tbuckley/cabot-search huggingface dataset:
Do Clinicians Know Which of Their Patients Have Central Venous Catheters?
Authors: Vineet Chopra, Sushant Govindan, Latoya Kuhn, David Ratz, Randy F. Sweis, Natalie Melin, Rachel Thompson, Aaron Tolan, James Barron, Sanjay Saint
Journal: Annals of Internal Medicine (2014)

Background: Complications associated with central venous catheters (CVCs) increase over time. Although early removal of unnecessary CVCs is important to prevent complications, the extent to which clinicians are aware that their patients have a CVC is unknown. Objective: To assess how often clinicians were unaware of the presence of triple-lumen catheters or peripherally inserted central catheters (PICCs) in hospitalized patients. Design: Multicenter, cross-sectional study. Setting: 3 academic medical centers in the United States. Patients: Hospitalized medical patients in intensive care unit (ICU) and non-ICU settings. Measurements: To ascertain awareness of CVCs, whether a PICC or triple-lumen catheter was present was determined; clinicians were then queried about device presence. Differences in device awareness among clinicians were assessed by chi-square tests. Results: 990 patients were evaluated, and 1881 clinician assessments were done. The overall prevalence of CVCs was 21.1% (n = 209), of which 60.3% (126 of 209) were PICCs. A total of 21.2% (90 of 425) of clinicians interviewed were unaware of the presence of a CVC. Unawareness was greatest among patients with PICCs, where 25.1% (60 of 239) of clinicians were unaware of PICC presence. Teaching attendings and hospitalists were more frequently unaware of the presence of CVCs than interns and residents (25.8% and 30.5%, respectively, vs. 16.4%). Critical care physicians were more likely to be aware of CVC presence than general medicine physicians (12.6% vs. 26.2%; P = 0.003). Limitations: Awareness was determined at 1 point in time and was not linked to outcomes. Patient length of stay and indication for CVC were not recorded. Conclusion: Clinicians are frequently unaware of the presence of PICCs and triple-lumen catheters in hospitalized patients. Further study of mechanisms that ensure that clinicians are aware of these devices so that they may assess their necessity seems warranted. Primary Funding Source: None.
Influence of the passive anisotropic properties on directional differences in propagation following modification of the sodium conductance in human atrial muscle. A model of reentry based on anisotropic discontinuous propagation.
Authors: M S Spach, P C Dolber, J F Heidlage
Journal: Circulation Research (1988)

Available models of circus movement reentry in cardiac muscle and of drug action on reentrant arrhythmias are based on continuous medium theory, which depends solely on the membrane ionic conductances to alter propagation. The purpose of this study is to show that the anisotropic passive properties at a microscopic level highly determine the propagation response to modification of the sodium conductance by premature action potentials and by sodium channel-blocking drugs. In young, uniform anisotropic atrial bundles, propagation of progressively earlier premature action potentials continued as a smooth process until propagation ceased simultaneously in all directions. In older, nonuniform anisotropic bundles, however, premature action potentials produced either unidirectional longitudinal conduction block or a dissociated zigzag type of longitudinal conduction (a safer type of propagation, similar to transverse propagation). Directional differences in the velocity of premature action potentials demonstrated that anisotropic propagation was necessary for a reentrant circuit to be contained within an area of 50 mm2, even with very short refractory periods. Quinidine produced Wenckebach periodicity, which disappeared after acetylcholine shortened the action potential. Quinidine also produced use-dependent dissociated zigzag longitudinal conduction in the older, nonuniform anisotropic bundles but not in the young, uniform anisotropic bundles. The electrophysiological consequence was that propagation events differed in an age-related manner in response to the same modification of the sodium conductance. The electrical events at microscopic level showed that conditions leading to obliteration of side-to-side electrical coupling between fibers (e.g., aging and chronic hypertrophy) provide a primary mechanism for reentry to occur within very small areas (1-2 mm) due to a variety of propagation phenomena that do not occur in tissues with tight electrical coupling in all directions.
The Cognitive Origins of Specific Types of Schizophrenic Speech Disturbances
Authors: Nancy M Docherty, Milton E Strauss, Thomas J Dinzeo, Annie St-Hilaire
Journal: American Journal of Psychiatry (2006)

Objective: Cognitive impairments associated with schizophrenia might be expected to have a marked impact on the ability to produce coherent speech, yet associations between cognitive performance and speech disorder have typically been weak. Findings on this question may have been limited by measurement methods and by the heterogeneity of speech disorder. This study examined the contributions of impairments in sustained attention and sequencing abilities to schizophrenic speech disorder, measured in terms of communication failures and divided into different types of disorder. Method: Samples of natural speech were collected from severely ill inpatients with schizophrenia and nonpsychiatric comparison subjects and rated for frequencies of six types of communication failures: four structural and two nonstructural types. Subjects also completed a battery of cognitive tests assessing several facets of attention and sequencing ability. Hierarchical regression was used to identify cognitive contributors to communication failures. Results: Impaired sustained attention was associated with more frequent structural and nonstructural communication failures. As predicted, impaired sequencing, and in particular conceptual sequencing, also made a substantial contribution to the structural communication failures, but not to the nonstructural ones. These findings held when global level of impairment was controlled statistically. Performance on the tests of attention and sequencing explained 56% of the variance in structural speech disorder. Conclusions: Schizophrenic speech disorder is heterogeneous in form and in cognitive underpinnings. Impairments in attention and sequencing abilities are highly predictive of communication failures related to language structure.
Osteocyte viability with glucocorticoid treatment: relation to histomorphometry
Authors: P N Sambrook
Journal: Annals of the Rheumatic Diseases (2003)

<b>Background:</b> Glucocorticoid induced osteoporosis is a common clinical problem. <b>Objective:</b> To determine the pathophysiology of glucocorticoid induced osteoarthritis at the organ level. <b>Methods:</b> Iliac crest biopsy specimens were obtained from nine patients receiving prednisone treatment for rheumatoid arthritis. Osteocyte viability and histomorphometric indices were assessed. <b>Results:</b> Compared with controls, glucocorticoid treated subjects had reduced trabecular thickness and increased erosion. The number of viable osteocytes was significantly decreased in glucocorticoid treated patients compared with controls. <b>Conclusion:</b> The impaired bone formation, increased erosion and, importantly, loss of viable osteocytes are all likely to contribute to the increased risk of fracture in these patients.
An Updated Overview on Wnt Signaling Pathways
Authors: Tata Purushothama Rao, Michael Kühl
Journal: Circulation Research (2010)

Abstract : Growth factor signaling is required for cellular differentiation, tissue morphogenesis, and tissue homeostasis. Misregulation of intracellular signal transduction can lead to developmental defects during embryogenesis or particular diseases in the adult. One family of growth factors important for these aspects is given by the Wnt proteins. In particular, Wnts have important functions in stem cell biology, cardiac development and differentiation, angiogenesis, cardiac hypertrophy, cardiac failure, and aging. Knowledge of growth factor signaling during differentiation will allow for improvement of targeted differentiation of embryonic or adult stem cells toward functional cardiomyocytes or for understanding the basis of diseases. Our major aim here is to provide a state of the art review summarizing our present knowledge of the intracellular Wnt-mediated signaling network. In particular, we provide evidence that the subdivision into canonical and noncanonical Wnt signaling pathways solely based on the identity of Wnt ligands or Frizzled receptors is not appropriate anymore. We thereby deliver a solid base for further upcoming articles of a review series focusing on the role of Wnt proteins on different aspects of cardiovascular development and dysfunction.
Maintenance of Tolerance by Regulation of Anti-myeloperoxidase B Cells
Authors: Donna O. Bunch, Jonathan S. Silver, Melanie C. Majure, Pamela Sullivan, David A. Alcorta, Hyunsook Chin, Susan L. Hogan, Yoshi I. Lindstrom, Stephen H. Clarke, Ronald J. Falk, Patrick H. Nachman
Journal: Journal of the American Society of Nephrology (2008)

Anti-neutrophil cytoplasmic autoantibodies directed toward myeloperoxidase or proteinase 3 are detected in sera of patients with small vessel vasculitis and participate in the pathogenesis of this disease. Autoantibodies develop when self-reactive B cells escape the regulation that ensures self-tolerance. In this study, regulation of anti-myeloperoxidase B cells was examined in mice that express an anti-myeloperoxidase Vkappa1C-Jkappa5 light-chain transgene, which confers anti-myeloperoxidase specificity when combined with a variety of heavy chains. Vkappa1C-Jkappa5 transgenic mice have splenic anti-myeloperoxidase B cells but do not produce circulating anti-myeloperoxidase antibodies. Two groups of transgenic mice that differed by their relative dosage of the transgene were compared; high-copy mice had a mean relative transgene dosage of 1.92 compared with 1.02 in the low-copy mice. These mice exhibited a 90 and 60% decrease in mature follicular B cells, respectively. High-copy mice were characterized by a large population of anti-myeloperoxidase B cells, a preponderance of B-1 cells, and an increased percentage of apoptotic myeloperoxidase-binding B cells. Low-copy mice had similar changes in B cell phenotype with the exception of an expanded marginal zone population. B cells from low-copy mice but not high-copy mice produced anti-myeloperoxidase antibodies after stimulation with lipopolysaccharide. These results indicate that tolerance to myeloperoxidase is maintained by central and peripheral deletion and that some myeloperoxidase-binding B cells are positively selected into the marginal zone and B-1 B cell subsets. A defect in these regulatory pathways could result in autoimmune disease.
Expression of recombinant genes in myocardium in vivo after direct injection of DNA.
Authors: H Lin, M S Parmacek, G Morle, S Bolling, J M Leiden
Journal: Circulation (1990)

The ability to program recombinant gene expression in cardiac myocytes in vivo holds promise for the treatment of many inherited and acquired cardiovascular diseases. In this report, we demonstrate that a recombinant beta-galactosidase gene under the control of the Rous sarcoma virus promoter can be introduced into and expressed in adult rat cardiac myocytes in vivo by the injection of purified plasmid DNA directly into the left ventricular wall. Cardiac myocytes expressing recombinant beta-galactosidase were detected histochemically in rat hearts for at least 4 weeks after injection of the beta-galactosidase gene. These results demonstrate the potential of this method of somatic gene therapy for the treatment of cardiovascular disease.
Mutation of FOXC1 and PITX2 induces cerebral small-vessel disease
Authors: Curtis R. French, Sudha Seshadri, Anita L. Destefano, Myriam Fornage, Corey R. Arnold, Philip J. Gage, Jonathan M. Skarie, William B. Dobyns, Kathleen J. Millen, Ting Liu, William Dietz, Tsutomu Kume, Marten Hofker, Derek J. Emery, Sarah J. Childs, Andrew J. Waskiewicz, Ordan J. Lehmann
Journal: Journal of Clinical Investigation (2014)

Patients with cerebral small-vessel disease (CSVD) exhibit perturbed end-artery function and have an increased risk for stroke and age-related cognitive decline. Here, we used targeted genome-wide association (GWA) analysis and defined a CSVD locus adjacent to the forkhead transcription factor FOXC1. Moreover, we determined that the linked SNPs influence FOXC1 transcript levels and demonstrated that patients as young as 1 year of age with altered FOXC1 function exhibit CSVD. MRI analysis of patients with missense and nonsense mutations as well as FOXC1-encompassing segmental duplication and deletion revealed white matter hyperintensities, dilated perivascular spaces, and lacunar infarction. In a zebrafish model, overexpression or morpholino-induced suppression of foxc1 induced cerebral hemorrhage. Inhibition of foxc1 perturbed platelet-derived growth factor (Pdgf) signaling, impairing neural crest migration and the recruitment of mural cells, which are essential for vascular stability. GWA analysis also linked the FOXC1-interacting transcription factor PITX2 to CSVD, and both patients with PITX2 mutations and murine Pitx2–/– mutants displayed brain vascular phenotypes. Together, these results extend the genetic etiology of stroke and demonstrate an increasing developmental basis for human cerebrovascular disease.
The Mechanism of Induction of Ovarian Tumors in the Mouse by 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene. I. Effect of Steroid Hormones and Carcinogen Concentration &lt;italic&gt;In Vivo&lt;/italic&gt;
Authors: Jull, J. W., Streeter, D. J., Sutherland, L.
Journal: JNCI Journal of the National Cancer Institute (1966)

Journal Article The Mechanism of Induction of Ovarian Tumors in the Mouse by 7,12-Dimethylbenz[a]anthracene. I. Effect of Steroid Hormones and Carcinogen Concentration In Vivo Get access J. W. Jull, J. W. Jull Cancer Research Centre, University of British Columbia, Vancouver, Canada, and Department of Experimental Pathology and Cancer Research, University of Leeds, Leeds, England Search for other works by this author on: Oxford Academic PubMed Google Scholar D. J. Streeter, D. J. Streeter Cancer Research Centre, University of British Columbia, Vancouver, Canada, and Department of Experimental Pathology and Cancer Research, University of Leeds, Leeds, England Search for other works by this author on: Oxford Academic PubMed Google Scholar L. Sutherland L. Sutherland Cancer Research Centre, University of British Columbia, Vancouver, Canada, and Department of Experimental Pathology and Cancer Research, University of Leeds, Leeds, England Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 37, Issue 4, October 1966, Pages 409–420, https://doi.org/10.1093/jnci/37.4.409 Published: 01 October 1966 Article history Received: 15 November 1965 Published: 01 October 1966
Preoperative measurement of segmental liver volume of donors for living related liver transplantation
Authors: Seiji Kawasaki, Masatoshi Makuuchi, Hidetoshi Matsunami, Yasuhiko Hashikura, Toshihiko Ikegami, Hisanao Chisuwa, Tatsuo Ikeno, Terumasa Noike, Tadatoshi Takayama, Hideo Kawarazaki
Journal: Hepatology (1993)

Segmental liver volume determination by computed tomographic scan was carried out preoperatively in nine donors for living related liver transplantation. The calculated volume was compared with the graft size actually obtained by three types of donor hepatectomy. The volume of the left lateral segment (175 to 241 ml) and the left lobe (310 to 490 ml) varied markedly among the donors. The ratio of the left lobar to total liver volume also showed a wide range of values (23.2% to 35.9%). The value of the left lobar volume did not correlate positively with the donor's body weight, suggesting that graft size cannot be predicted only on the basis of the donor's body size. Segmental graft liver volume was estimated by use of computed tomographic scan, with acceptable accuracy on comparison with the graft volume actually obtained. In living related liver transplantation, the type of donor hepatectomy should be selected on the basis of the segmental liver volume of the donor in addition to the recipient's body size so that liver failure can be prevented in recipients and the donor's safety can be assured as far as possible.
Risk factors in the pregnancy of patients with systemic lupus erythematosus: association of hypocomplementaemia with poor prognosis.
Authors: S Shibata, T Sasaki, Y Hirabayashi, J Seino, K Okamura, K Yoshinaga, N Morito, R Kasukawa, S Aotuka, R Yokohari
Journal: Annals of the Rheumatic Diseases (1992)

Fetal wastage is still high in the pregnancies of patients with systemic lupus erythematosus (SLE). We examined retrospectively the cases of 38 patients with inactive SLE in whom pregnancy was either desired or had already been obtained. The prevalence of antiphospholipid antibodies in the group with fetal loss was high. The antibodies were, however, also detected in five of 14 patients who had had a live birth. It was noted that low levels of serum complement activity (CH50 less than 25 U/ml) occurred in five of six patients with fetal loss, but in only two of 22 with a live birth. Serial studies also confirmed a close association between decreased serum complement activity and poor fetal prognosis in lupus pregnancy. Treatment with increased doses of prednisolone may help to achieve successful live births. Thus hypocomplementaemia may be associated with a worse prognosis for the fetus in the pregnancies of some patients with SLE in remission.
Phase III Trials of Targeted Anticancer Therapies: Redesigning the Concept
Authors: Alberto Ocana, Eitan Amir, Francisco Vera-Badillo, Bostjan Seruga, Ian F. Tannock
Journal: Clinical Cancer Research (2013)

Randomized phase III trials provide the gold-standard evidence for the approval of new drugs: an experimental treatment is compared with the current standard of care to identify clinically relevant differences in a predefined endpoint. However, there are several problems relating to the current role of phase III trials in drug development including the limited clinical benefit observed for some approved agents, the necessity for large trials to detect these differences, the inability of such trials to identify rare but important toxicities, and high cost. The design of phase III trials evaluating drug combinations, and those including biomarkers, presents additional challenges. Here, we review these problems and suggest that phase III trials with adaptive designs in selected prescreened populations could reduce these limitations.
A novel isoform of the Ly108 gene ameliorates murine lupus
Authors: Marton Keszei, Cynthia Detre, Svend T. Rietdijk, Pilar Muñoz, Xavier Romero, Scott B. Berger, Silvia Calpe, Gongxian Liao, Wilson Castro, Aimee Julien, Ying-Yu Wu, Dong-Mi Shin, Jaime Sancho, Mercedes Zubiaur, Herbert C. Morse, Laurence Morel, Pablo Engel, Ninghai Wang, Cox Terhorst
Journal: The Journal of Experimental Medicine (2011)

Studies of human systemic lupus erythematosus patients and of murine congenic mouse strains associate genes in a DNA segment on chromosome 1 with a genetic predisposition for this disease. The systematic analysis of lupus-prone congenic mouse strains suggests a role for two isoforms of the Ly108 receptor in the pathogenesis of the disease. In this study, we demonstrate that Ly108 is involved in the pathogenesis of lupus-related autoimmunity in mice. More importantly, we identified a third protein isoform, Ly108-H1, which is absent in two lupus-prone congenic animals. Introduction of an Ly108-H1–expressing transgene markedly diminishes T cell–dependent autoimmunity in congenic B6.Sle1b mice. Thus, an immune response–suppressing isoform of Ly108 can regulate the pathogenesis of lupus.
Time gated fluorescence spectroscopy in Barrett's oesophagus
Authors: M-A E J Ortner
Journal: Gut (2002)

<b>Background and aims:</b> Specialised intestinal metaplasia and its dysplastic transformation, which precedes cancer in Barrett's oesophagus cannot be differentiated in standard gastroscopy. The aim of this study was to investigate whether laser induced protoporphyrin IX fluorescence permits the detection of specialised intestinal metaplasia and dysplasia during endoscopy and to take biopsy specimens in a guided rather than random manner. <b>Methods:</b> In 53 patients with Barrett's oesophagus 5-aminolaevulinic acid was sprayed on the mucosa. Approximately 60 to 120 minutes later, biopsy specimens were taken based on point-like measurements of delayed fluorescence intensity ratios of protoporphyrin IX in vivo. Two independent pathologists examined the 596 biopsy specimens taken, 168 of which were selected to be investigated by a third pathologist. Among these specimens only those (n=141) with a consensus diagnosis by at least two pathologists and p53 expression as additional marker were included in the analysis. <b>Results:</b> The median of normalised fluorescence intensity (ratio of delayed PpIX fluorescence intensity to immediate autofluorescence intensity) in non-dysplastic specialised intestinal metaplasia (0.51, 68% CI 0.09 to 1.92) and low grade dysplasia (1.89, 68% CI 0.55 to 3.92) differed significantly (p&lt;0.005). Dysplasia was detected at a rate 2.8-fold higher compared with screening endoscopy despite taking fewer specimens. In addition, three early cancers were detected for the first time. Moreover, this method permitted differentiation of specialised intestinal metaplasia from junctional or gastric-fundic type epithelium (p&lt;0.013). <b>Conclusions:</b> For the first time it was possible to differentiate low grade dysplasia from non-dysplastic Barrett's mucosa during endoscopy based on delayed laser induced fluorescence endoscopy of PpIX. Furthermore, the method helps to detect specialised intestinal metaplasia in short Barrett's oesophagus.