tbuckley/cabot-search huggingface dataset:
The diagnosis of subclinical hepatic encephalopathy in patients with cirrhosis using neuropsychological tests and automated electroencephalogram analysis
Authors: J C Quero, I J Hartmann, J Meulstee, W C Hop, S W Schalm
Journal: Hepatology (1996)

Neuropsychological tests used for the assessment of subclinical hepatic encephalopathy (SHE) may overdiagnose SHE because scores are usually not corrected for age. The aim of this study was to estimate the prevalence of SHE using two easy administrable psychometric tests (Number Connection Test part A [NCT–A], Symbol Digit Test [SDT]) with age–related normal values. In addition, spectral electroencephalogram (EEG) was used, which is the in–house electrophysiological method for quantifying encephalopathy. One hundred and thirty–seven consecutive patients (mean age 49 years, range 17–77) with cirrhosis without any clinical signs of encephalopathy, were screened for SHE. In addition, the Child–Pugh score and the arterial blood ammonia were determined. Patients with concurrent use of alcohol, benzodiazepines or anti–epileptics were excluded. Fifty percent of the patients had an abnormal NCT according to the standard recommended procedure, in contrast only 7% of the patients had an abnormal NCT when scores corrected for age were used. Combining the results of the spectral EEG and the psychometric tests corrected for age yielded a higher prevalence of SHE (23%) than when each test method was used alone (17% vs. 10% abnormal, respectively). Severity of liver disease correlated with the presence of SHE, because the prevalence of abnormal tests increased from 14% in Child–Pugh grade A to 45% in Child–Pugh grade B or C. Age above 40 years and an elevated blood ammonia level were significant determinants related to an abnormal EEG. We conclude that the NCT uncorrected for age markedly overdiagnoses SHE and, therefore, should not be used as a test for the screening of SHE. Using a combination of spectral EEG and two psychometric tests with age–corrected normal values a low prevalence of SHE in patients with Child A liver cirrhosis is found. Older patients with an elevated arterial ammonia are more prone to develop SHE than younger patients with an equal arterial ammonia concentration.
Plaque Instability Frequently Occurs Days or Weeks Before Occlusive Coronary Thrombosis
Authors: Saskia Z.H. Rittersma, Allard C. van der Wal, Karel T. Koch, Jan J. Piek, José P.S. Henriques, Karla J. Mulder, Johanna P.H.M. Ploegmakers, Martin Meesterman, Robbert J. de Winter
Journal: Circulation (2005)

Acute ST-elevation myocardial infarction (STEMI) is caused by sudden occlusive coronary thrombosis, after plaque disruption; however, a considerable time interval between plaque disturbance and the onset of symptoms has been suggested. We therefore studied the age of intracoronary thrombi, aspirated during angioplasty in patients with acute STEMI.Percutaneous intracoronary thrombectomy during angioplasty was performed in 211 consecutive STEMI patients within 6 hours after onset of anginal symptoms. The aspirated material was histologically screened on thrombus and plaque components, and thrombus age was classified as fresh (<1 day), lytic thrombus (1 to 5 days), and organized thrombus (>5 days). In all patients, intracoronary-derived material was retrieved in the filter of the collection bottle. Thrombus was identified in 199 (95%) of 211 patients. In 12 patients (5%), only plaque components were identified, and in 85 patients (41%), both thrombus and plaque material were aspirated. In 18 (9%) of 199 patients, the thrombus was organized, and in 70 patients (35%), the thrombus showed lytic changes, whereas in 98 (49%), a completely fresh thrombus was found. In 14 (7%) of 199 patients, the thrombus showed combined features of both fresh thrombus and organized thrombus.In at least 50% of patients with acute STEMI, coronary thrombi were days or weeks old. This indicates that sudden coronary occlusion is often preceded by a variable period of plaque instability and thrombus formation, initiated days or weeks before onset of symptoms.
A Catastrophic Presentation of Adult Croup
Authors: Tanyalak Parimon, Nirmal B. Charan, David K. Anderson, Paula G. Carvalho
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Figure 1. (A) Chest radiograph upon arrival to the emergency department. (B) A magnified view of airway section of chest radiograph to demonstrate “steeple sign” (a tapering of subglottic airway) indicating airway narrowing as marked by arrow. Figure 2. Computed tomography neck without contrast at the level of the arytenoid cartilages after intubation showing complete obliteration around the endotracheal tube (arrow) of airway at the level of glottis, and below (seen in other images).
An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis.
Authors: N H Ruddle, C M Bergman, K M McGrath, E G Lingenheld, M L Grunnet, S J Padula, R B Clark
Journal: The Journal of Experimental Medicine (1990)

Uncertainty regarding pathogenic mechanisms has been a major impediment to effective prevention and treatment for human neurologic diseases such as multiple sclerosis, tropical spastic paraparesis, and AIDS demyelinating disease. Here, we implicate lymphotoxin (LT) (tumor necrosis factor beta [TNF-beta]) and TNF-alpha in experimental allergic encephalomyelitis (EAE), a murine model of an autoimmune demyelinating disease. In this communication, we report that treatment of recipient mice with an antibody that neutralizes LT and TNF-alpha prevents transfer of clone-mediated EAE. LNC-8, a myelin basic protein-specific T cell line, produces high levels of LT and TNF-alpha after activation by concanavalin A, antibody to the CD-3 epsilon component of the T cell receptor, or myelin basic protein presented in the context of syngeneic spleen cells. LNC-8 cells transfer clinical signs of EAE. When LNC-8 recipient mice were also treated with TN3.19.12, a monoclonal antibody that neutralizes LT and TNF-alpha, the severity of the transferred EAE was reduced, while control antibodies did not alter the disease. The effect of anti-LT/TNF-alpha treatment was long lived and has been sustained for 5 mo. These findings suggest that LT and TNF-alpha and the T cells that produce them play an important role in EAE.
Increase in positive selection of CD8+ T cells in TAP1-mutant mice by human beta 2-microglobulin transgene.
Authors: H Martien van Santen, A Woolsey, P G Rickardt, L Van Kaer, E J Baas, A Berns, S Tonegawa, H L Ploegh
Journal: The Journal of Experimental Medicine (1995)

Mice harboring a deletion of the gene encoding the transporter associated with antigen presentation-1 (TAP1) are impaired in providing major histocompatibility complex (MHC) class I molecules with peptides of cytosolic origin and lack stable MHC class I cell surface expression. They consequently have a strongly reduced number of CD8+ T cells. To examine whether selection of CD8+ T cells is dependent on TAP-dependent peptides, we partially restored MHC class I cell surface expression in TAP1-deficient mice by introduction of human beta 2-microglobulin. We show that selection of functional CD8+ T cells can be augmented in vivo in the absence of TAP1-dependent peptides.
Which Factors Influence Psychiatrists’ Selection of Antidepressants?
Authors: Mark Zimmerman, Michael Posternak, Michael Friedman, Naureen Attiullah, Scott Baymiller, Robert Boland, Stacie Berlowitz, Shahzad Rahman, Kirsten Uy, Steve Singer
Journal: American Journal of Psychiatry (2004)

There is little empirical evidence to guide clinicians in choosing among the diverse array of antidepressants available. In the absence of replicated empirical research guiding the selection of antidepressants, it is of interest to examine what factors psychiatrists consider when prescribing antidepressants.For 1,137 depressed patients who received a new antidepressant prescription, the treating psychiatrist completed a 43-item questionnaire listing factors that might have influenced the choice of antidepressant medication. The questionnaire was filled out immediately after an antidepressant was prescribed to treat a depressive disorder.The most common factors influencing antidepressant selection were the avoidance of specific side effects, the presence of comorbid psychiatric disorders, and the presence of specific clinical symptoms. Prior treatment history, including prior positive or failed response to a drug, was the next most frequently endorsed factor influencing medication choice. Some factors that have been commonly discussed in the literature, such as concern about discontinuation syndrome and drug-drug interactions, rarely influenced antidepressant selection.Because relatively little research has examined clinical features associated with differential response to the newer generation of antidepressants, a study of psychiatrists' prescribing practices highlights priorities for future controlled research. Our results suggest that two priority areas are the treatment of depression with coexisting anxiety symptoms/anxiety disorders and the influence of particular symptoms on response to different medications.
Understanding the natural progression in %FEV<sub>1</sub>decline in patients with cystic fibrosis: a longitudinal study
Authors: David Taylor-Robinson, Margaret Whitehead, Finn Diderichsen, Hanne Vebert Olesen, Tania Pressler, Rosalind L Smyth, Peter Diggle
Journal: Thorax (2012)

<h3>Background</h3> Forced expiratory volume in 1 s as a percentage of predicted (%FEV<sub>1</sub>) is a key outcome in cystic fibrosis (CF) and other lung diseases. As people with CF survive for longer periods, new methods are required to understand the way %FEV<sub>1</sub> changes over time. An up to date approach for longitudinal modelling of %FEV<sub>1</sub> is presented and applied to a unique CF dataset to demonstrate its utility at the clinical and population level. <h3>Methods and findings</h3> The Danish CF register contains 70 448 %FEV<sub>1</sub> measures on 479 patients seen monthly between 1969 and 2010. The variability in the data is partitioned into three components (between patient, within patient and measurement error) using the empirical variogram. Then a linear mixed effects model is developed to explore factors influencing %FEV<sub>1</sub> in this population. Lung function measures are correlated for over 15 years. A baseline %FEV<sub>1</sub> value explains 63% of the variability in %FEV<sub>1</sub> at 1 year, 40% at 3 years, and about 30% at 5 years. The model output smooths out the short-term variability in %FEV<sub>1</sub> (SD 6.3%), aiding clinical interpretation of changes in %FEV<sub>1</sub>. At the population level significant effects of birth cohort, pancreatic status and <i>Pseudomonas aeruginosa</i> infection status on %FEV<sub>1</sub> are shown over time. <h3>Conclusions</h3> This approach provides a more realistic estimate of the %FEV<sub>1</sub> trajectory of people with chronic lung disease by acknowledging the imprecision in individual measurements and the correlation structure of repeated measurements on the same individual over time. This method has applications for clinicians in assessing prognosis and the need for treatment intensification, and for use in clinical trials.
Prasugrel versus Clopidogrel for Acute Coronary Syndromes without Revascularization
Authors: Matthew T. Roe, Paul W. Armstrong, Keith A.A. Fox, Harvey D. White, Dorairaj Prabhakaran, Shaun G. Goodman, Jan H. Cornel, Deepak L. Bhatt, Peter Clemmensen, Felipe Martinez, Diego Ardissino, Jose C. Nicolau, William E. Boden, Paul A. Gurbel, Witold Ruzyllo, Anthony J. Dalby, Darren K. McGuire, Jose L. Leiva-Pons, Alexander Parkhomenko, Shmuel Gottlieb, Gracita O. Topacio, Christian Hamm, Gregory Pavlides, Assen R. Goudev, Ali Oto, Chuen-Den Tseng, Bela Merkely, Vladimir Gasparovic, Ramon Corbalan, Mircea Cinteză, R. Craig McLendon, Kenneth J. Winters, Eileen B. Brown, Yuliya Lokhnygina, Philip E. Aylward, Kurt Huber, Judith S. Hochman, E. Magnus Ohman
Journal: New England Journal of Medicine (2012)

The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated.In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel.At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P=0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P=0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group.Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).
Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013
Authors: D. Papamichael, R.A. Audisio, B. Glimelius, A. de Gramont, R. Glynne-Jones, D. Haller, C.-H. Köhne, S. Rostoft, V. Lemmens, E. Mitry, H. Rutten, D. Sargent, J. Sastre, M. Seymour, N. Starling, E. Van Cutsem, M. Aapro
Journal: Annals of Oncology (2014)
Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies.
Authors: G A Schellekens, B A de Jong, F H van den Hoogen, L B van de Putte, W J van Venrooij
Journal: Journal of Clinical Investigation (1998)

Only a few autoantibodies that are more or less specific for RA have been described so far. The rheumatoid factor most often tested for is not very specific for RA, while the more specific antiperinuclear factor for several reasons is not routinely used as a serological parameter. Here we show that autoantibodies reactive with synthetic peptides containing the unusual amino acid citrulline, a posttranslationally modified arginine residue, are specifically present in the sera of RA patients. Using several citrulline-containing peptide variants in ELISA, antibodies could be detected in 76% of RA sera with a specificity of 96%. Sera showed a remarkable variety in the reactivity pattern towards different citrulline-containing peptides. Affinity-purified antibodies were shown to be positive in the immunofluorescence-based antiperinuclear factor test, and in the so-called antikeratin antibody test, and were reactive towards filaggrin extracted from human epidermis. The specific nature of these antibodies and the presence of these antibodies early in disease, even before other disease manifestations occur, are indicative for a possible role of citrulline-containing epitopes in the pathogenesis of RA.
Outcomes and Cost of Outpatient or Inpatient Management of 712 Patients With Febrile Neutropenia
Authors: Linda S. Elting, Charles Lu, Carmelita P. Escalante, Sharon H. Giordano, Jonathan C. Trent, Catherine Cooksley, Elenir B.C. Avritscher, Ya-Chen Tina Shih, Joe Ensor, B. Nebiyou Bekele, Richard J. Gralla, James A. Talcott, Kenneth Rolston
Journal: Journal of Clinical Oncology (2008)

We retrospectively compared the outcomes and costs of outpatient and inpatient management of low-risk outpatients who presented to an emergency department with febrile neutropenia (FN).A single episode of FN was randomly chosen from each of 712 consecutive, low-risk solid tumor outpatients who had been treated prospectively on a clinical pathway (1997-2003). Their medical records were reviewed retrospectively for overall success (resolution of all signs and symptoms of infection without modification of antibiotics, major medical complications, or intensive care unit admission) and nine secondary outcomes. Outcomes were assessed by physician investigators who were blinded to management strategy. Outcomes and costs (payer's perspective) in 529 low-risk outpatients were compared with 123 low-risk patients who were psychosocially ineligible for outpatient management (no access to caregiver, telephone, or transportation; residence > 30 minutes from treating center; poor compliance with previous outpatient therapy) using univariate statistical tests.Overall success was 80% among low-risk outpatients and 79% among low-risk inpatients. Response to initial antibiotics was 81% among outpatients and 80% among inpatients (P = .94); 21% of those initially treated as outpatients subsequently required hospitalization. All patients ultimately responded to antibiotics; there were no deaths. Serious complications were rare (1%) and equally frequent between the groups. The mean cost of therapy among inpatients was double that of outpatients ($15,231 v $7,772; P < .001).Outpatient management of low-risk patients with FN is as safe and effective as inpatient management of low-risk patients and is significantly less costly.
Mice deficient in α-actinin-4 have severe glomerular disease
Authors: Claudine H. Kos, Tu Cam Le, Sumita Sinha, Joel M. Henderson, Sung Han Kim, Hikaru Sugimoto, Raghu Kalluri, Robert E. Gerszten, Martin R. Pollak
Journal: Journal of Clinical Investigation (2003)

Dominantly inherited mutations in ACTN4, which encodes α-actinin-4, cause a form of human focal and segmental glomerulosclerosis (FSGS). By homologous recombination in ES cells, we developed a mouse model deficient in Actn4. Mice homozygous for the targeted allele have no detectable α-actinin-4 protein expression. The number of homozygous mice observed was lower than expected under mendelian inheritance. Surviving mice homozygous for the targeted allele show progressive proteinuria, glomerular disease, and typically death by several months of age. Light microscopic analysis shows extensive glomerular disease and proteinaceous casts. Electron microscopic examination shows focal areas of podocyte foot-process effacement in young mice, and diffuse effacement and globally disrupted podocyte morphology in older mice. Despite the widespread distribution of α-actinin-4, histologic examination of mice showed abnormalities only in the kidneys. In contrast to the dominantly inherited human form of ACTN4-associated FSGS, here we show that the absence of α-actinin-4 causes a recessive form of disease in mice. Cell motility, as measured by lymphocyte chemotaxis assays, was increased in the absence of α-actinin-4. We conclude that α-actinin-4 is required for normal glomerular function. We further conclude that the nonsarcomeric forms of α-actinin (α-actinin-1 and α-actinin-4) are not functionally redundant. In addition, these genetic studies demonstrate that the nonsarcomeric α-actinin-4 is involved in the regulation of cell movement.
The anti-inflammatory effects of adiponectin are mediated via a heme oxygenase-1-dependent pathway in rat Kupffer cells
Authors: Palash Mandal, Pil‐Hoon Park, Megan R. McMullen, Brian T. Pratt, Laura E. Nagy
Journal: Hepatology (2009)

Altered expression and activity of immunomodulatory cytokines plays a major role in the pathogenesis of alcoholic liver disease. Chronic ethanol feeding increases the sensitivity of Kupffer cells, the resident hepatic macrophage, to lipopolysaccharide (LPS), leading to increased tumor necrosis factor alpha (TNF-α) expression. This sensitization is normalized by treatment of primary cultures of Kupffer cells with adiponectin, an anti-inflammatory adipokine. Here we tested the hypothesis that adiponectin-mediated suppression of LPS signaling in Kupffer cells is mediated via an interleukin-10 (IL-10)/heme oxygenase-1 (HO-1) pathway after chronic ethanol feeding. Knockdown of IL-10 expression in primary cultures of Kupffer cells with small interfering RNA (siRNA) prevented the inhibitory effect of globular adiponectin (gAcrp) on LPS-stimulated TNF-α expression. gAcrp increased IL-10 mRNA and protein expression, as well as expression of the IL-10 inducible gene, HO-1; expression was higher in Kupffer cells from ethanol-fed rats compared with pair-fed controls. Although IL-10 receptor surface expression on Kupffer cells was not affected by ethanol feeding, IL-10–mediated phosphorylation of STAT3 and expression of HO-1 was higher in Kupffer cells after ethanol feeding. Inhibition of HO-1 activity, either by treatment with the HO-1 inhibitor zinc protoporphyrin or by siRNA knockdown of HO-1, prevented the inhibitory effect of gAcrp on LPS-stimulated TNF-α expression in Kupffer cells. LPS-stimulated TNF-α expression in liver was increased in mice after chronic ethanol exposure. When mice were treated with cobalt protoporphyrin to induce HO-1 expression, ethanol-induced sensitivity to LPS was ameliorated. Conclusion: gAcrp prevents LPS-stimulated TNF-α expression in Kupffer cells through the activation of the IL-10/STAT3/HO-1 pathway. Kupffer cells from ethanol-fed rats are highly sensitive to the anti-inflammatory effects of gAcrp; this sensitivity is associated with both increased expression and sensitivity to IL-10. (HEPATOLOGY 2010.)
Clinical value of bile salt tests in anicteric liver disease.
Authors: J G Douglas, G J Beckett, I A Nimmo, N D Finlayson, I W Percy-Robb
Journal: Gut (1981)

Fasting and postprandial serum bile salt concentrations and intravenous glycocholate disappearance were studied in 20 patients with anicteric liver disease who had only minor abnormalities of conventional liver function tests. Abnormalities in the fasting or two hour postprandial conjugated cholate concentrations were found in all but one of the patients who had an abnormality in bilirubin concentration. In these patients, fasting and postprandial conjugated cholate concentrations were raised on average three and two times respectively above the upper limit of the reference range, while bilirubin concentration was raised only 50%. Postprandial conjugated cholate concentrations were also abnormal in two patients with normal bilirubin concentrations. Measurement of fasting and postprandial conjugated chenodeoxycholate concentration and intravenous glycocholate disappearance proved less informative than the fasting and postprandial conjugated cholate test. These results suggest that, where bilirubin concentrations are normal or only slightly raised, measurement of serum fasting and two hour postprandial conjugated cholate concentrations may prove helpful in the detection of minor abnormalities in hepatic anion transport.
Prognostic relevance of P-glycoprotein expression in breast cancer
Authors: S.C. Linn, G. Giaccone, P.J. van Diest, W.M.D. Blokhuis, P. van der Valk, C.K. van Kalken, C.M. Kuiper, H.M. Pinedo, J.P.A. Baak
Journal: Annals of Oncology (1995)