tbuckley/cabot-search huggingface dataset:
Prevalence, extent and composition of coronary plaque in patients with rheumatoid arthritis without symptoms or prior diagnosis of coronary artery disease
Authors: George A Karpouzas, Jennifer Malpeso, Tae-Young Choi, Dong Li, Silvia Munoz, Matthew J Budoff
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Accelerated cardiovascular morbidity and mortality occur in patients with rheumatoid arthritis (RA). We evaluated the presence, burden and compositional differences of coronary plaque in patients with RA without symptoms or diagnosis of coronary artery disease (CAD) compared against controls. <h3>Methods</h3> One hundred and fifty patients with RA and 150 matched controls underwent 64-slice CT angiography (CTA) for evaluation of coronary plaque. Numbers of segments with plaque per patient (Segment involvement score (SIS)), degree of segment stenosis (stenosis severity score (SSS)), plaque size (plaque burden score (PBS)), and composition were assessed using a standardised American Heart Association 15-segment model. Lesions were classified as non-calcified plaque (NCP), mixed (MP), and fully calcified plaque (CP). <h3>Results</h3> &nbsp;Higher proportion of patients with RA had plaque when compared with controls (71% vs 45%, p&lt;0.0001); 13.5% of total RA segments harboured plaque compared with 6% in controls (p&lt;0.0001), and all plaque types were higher (p&lt;0.001). Multivessel disease, both non-obstructive and obstructive, was more prevalent, and quantitative measures of stenotic plaque severity (SSS) and extent (PBS) were higher in RA, even after adjustments for cardiac risk factors (p&lt;0.01 for all). A steeper progression of plaque with age was seen in RA. Disease activity associated only with presence of NCP and MP, whereas patient age was the only predictor of fully CP. <h3>Conclusions</h3> RA patients without CAD have higher prevalence, extent, and severity of all types of coronary plaque. Residual disease activity associates with presence of higher risk NCP and MP potentially contributing to future adverse cardiac events.
Tremor and clinical fluctuation are related to sleep disorders in Chinese patients with Parkinson’s disease
Authors: Hongyan Zhou, Cunzhou Shen, Jie Chen, Hao Qian, Yifan Zheng, Yanmei Liu, Wenbiao Xian, Zhong Pei, Ling Chen
Journal: Translational Neurodegeneration (2014)

To study the relationship between sleep disturbances and symptoms in patients with Parkinson's disease (PD).The Parkinson's Disease Sleep Scale-Chinese Version (PDSS-CV) was used to evaluate the sleep disturbances of PD patients in a cross sectional study. The Unified Parkinson's Disease Rating Scale (UPDRS) parts II-IV, and the Hoehn & Yahr (H&Y) stage were used to determine the level of motor function in PD and the severity of PD. The Spearman correlation and a multiple regression analysis were used to identify the relationship between sleep disturbances and symptoms of PD. The quantities derived from the UPDRS and the H&Y stage and disease duration were compared between groups of patients either with or without sleep disturbances identified by the PDSS. This study was conducted from December 2011 to March 2012 at the First Affiliated Hospital of Sun Yat-sen University, in Guangzhou.A total of 136 PD patients were included in this study. The overall total PDSS score in PD patients was 107.58 ± 23.35 points (range: 30-146). There were significant differences in the disease duration, the H&Y stage, and the UPDRS section subscores between groups of patients either with or without sleep disturbances (Kruskal-Wallis Test, p <0.05). There were significant negative correlations between PDSS scores and the UPDRS subscores, the H&Y stage and the disease duration (Spearman correlation, p < 0.05). The multiple regression analysis indicated that sleep disturbances identified by the PDSS were only associated with daily life activity, tremor intensity and clinical fluctuation (R(2) = 0.22, F(3,132) = 12.4, p < 0.001). The correlations were also significant when the contribution of the other two factors was excluded using partial correlations.The level of daily life activity and the occurrences of tremor and clinical fluctuation are likely to be important factors that lead to PD patients' sleep disturbances. This study may elucidate an important clue for the relationship between sleep disturbances and PD symptoms.
Residual HIV-1 RNA in Blood Plasma of Patients Taking Suppressive Highly Active Antiretroviral Therapy
Authors: G Dornadula, H Zhang, B VanUitert, J Stern, L Livornese, M J Ingerman, J Witek, R J Kedanis, J Natkin, J DeSimone, R J Pomerantz
Journal: JAMA (1999)

ContextDespite suppressive treatment with highly active antiretroviral therapy (HAART), replication-competent virus can still be isolated from peripheral blood mononuclear cells and genital cells of many individuals receiving suppressive HAART.ObjectiveTo determine whether free virion RNA can be detected in the blood plasma and/or genital tract fluids from patients receiving suppressive HAART.DesignProspective cohort study conducted from November 1998 to May 1999.SettingAcademic medical center.PatientsHuman immunodeficiency virus 1–infected individuals (20 men and 2 women) shown in our laboratories to have fewer than 50 copies/mL of HIV-1 RNA in peripheral blood plasma while taking suppressive HAART.Main Outcome MeasuresFree virion RNA levels in peripheral blood plasma and genital fluids, quantified using an ultrasensitive reverse transcriptase polymerase chain reaction able to quantify cell-free virion RNA to a lower limit of 5 copies/mL and qualitatively detect viral RNA below this level.ResultsIn all 22 patients, residual viral RNA could be detected in the peripheral blood plasma (mean level, 17 copies/mL). The presence of viral RNA suggests that ongoing viral replication is occurring, albeit at low levels, in each patient evaluated. Viral RNA levels were lower in most patients' genital fluids compared with blood plasma and in 12 patients were undetectable.ConclusionsThese data suggest that low-level replication of HIV-1 in patients taking suppressive HAART may be demonstrated not only in peripheral blood mononuclear cells but also in peripheral plasma as cell-free virion RNA. Complete ablation of viral replication may require intensification of antiretroviral therapies beyond standard suppressive HAART.
Reference equations for lung function screening of healthy never-smoking adults aged 18-80 years
Authors: S. P. Kuster, D. Kuster, C. Schindler, M. K. Rochat, J. Braun, L. Held, O. Brändli
Journal: European Respiratory Journal (2007)

The need for updated spirometric reference values to be used on European populations is widely acknowledged, especially for subjects aged &gt;70 yrs. Their reference values are generally based on extrapolations. The aim of the present study was to calculate reference values for lung function screening of healthy, never-smoking adults aged 18–80 yrs and to compare them with the most widely used reference equations. Results of screening spirometry of 8,684 healthy, never-smoking adults were used to calculate mean values and fifth percentiles of lung function variables. The European Community of Coal and Steel (ECCS) reference equations underestimate forced expiratory volume in one second (FEV 1 ) and forced vital capacity (FVC). For example, in 50-yr-old males (height 175 cm), lower limits of normal for FEV 1 are underestimated by 198 mL, and for FVC by 210 mL. In 50-yr-old females (height 165 cm), lower limits of normal for FEV 1 are underestimated by 191 mL, and for FVC by 270 mL. The decline of FVC in elderly subjects is steeper than predicted by the ECCS. Reference equations derived from spirometry data locally collected in a practical setting by well-trained personnel might be more appropriate for everyday use than generally used equations based on data from scientific studies in the distant past.
The Toxoplasma Pseudokinase ROP5 Forms Complexes with ROP18 and ROP17 Kinases that Synergize to Control Acute Virulence in Mice
Authors: Ronald D. Etheridge, Aditi Alaganan, Keliang Tang, Hua Jane Lou, Benjamin E. Turk, L. David Sibley
Journal: Cell Host & Microbe (2014)
Percutaneous Coronary Interventions in Facilities Without Cardiac Surgery On Site: A Report From the National Cardiovascular Data Registry (NCDR)
Authors: Michael A. Kutcher, Lloyd W. Klein, Fang-Shu Ou, Thomas P. Wharton, Gregory J. Dehmer, Mandeep Singh, H. Vernon Anderson, John S. Rumsfeld, William S. Weintraub, Richard E. Shaw, Matthew T. Sacrinty, Albert Woodward, Eric D. Peterson, Ralph G. Brindis
Journal: Journal of the American College of Cardiology (2009)
Microsatellite instability and mutation analysis among southern Italian patients with colorectal carcinoma: detection of different alterations accounting for MLH1 and MSH2 inactivation in familial cases
Authors: M. Colombino, A. Cossu, A. Arba, A. Manca, A. Curci, A. Avallone, G. Comella, G. Botti, F. Scintu, M. Amoruso, D. D’Abbicco, M.R. d’Agnessa, A. Spanu, F. Tanda, G. Palmieri
Journal: Annals of Oncology (2003)
Cardiac and pulmonary norepinephrine release and removal in the dog.
Authors: P A Blombery, B G Heinzow
Journal: Circulation Research (1983)

Norepinephrine extraction and spillover rates were determined in the heart and lungs of anesthetized dogs under resting conditions, during sympathetic stimulation, and during epicardial pacing. The fractional extraction of norepinephrine across the coronary and pulmonary vascular beds was measured from the venoarterial difference in tritiated norepinephrine after infusion of a tracer dose to a steady state level. Cardiac extraction averaged 0.299 +/- 0.03 and pulmonary extraction averaged 0.215 +/- 0.014; extraction was unaffected by sympathetic stimulation or pacing. Norepinephrine spillover from sympathetic nerve terminals in the heart and lungs was measured from the venoarterial difference in endogenous norepinephrine and plasma flow after correction for the extraction component. Cardiac norepinephrine spillover increased linearly with increasing frequency of sympathetic stimulation to 7.44 times resting levels at 2 Hz. During pacing, there was no change in cardiac norepinephrine spillover despite marked changes in heart rate. Norepinephrine spillover was demonstrated under resting conditions in the lung and was greater than observed in the heart. Pulmonary norepinephrine spillover increased with sympathetic stimulation to 4.15 times resting levels at 2 Hz. It is possible to separate the contributions of norepinephrine extraction and spillover to measured venoarterial differences of norepinephrine under physiological conditions in the dog.
THE PATHOGENESIS OF WAXY DEGENERATION OF STRIATED MUSCLES (ZENKER'S DEGENERATION)
Authors: H. Gideon Wells
Journal: The Journal of Experimental Medicine (1909)

In view of theoretical deductions and the positive results obtained in the above experiments, it would seem probable that the production of waxy degeneration depends upon the action of lactic acid which is formed by the living muscle under the stimulation of infecting bacteria or their toxins, the formation of large amounts of lactic acid and its accumulation being perhaps favored by defective circulation through the injured muscle. The hyaline transformation of muscle acted upon by lactic acid is analogous to the swelling of fibrin placed in dilute acids. This view is supported by both negative and positive experimental evidence—the negative evidence being that simple anemic necrosis, aseptic or antiseptic autolysis whether in vivo or in vitro, or the action of bacteria of various sorts on muscle in vitro, are all incapable of causing changes in muscle cells resembling those characteristic of waxy or hyaline degeneration of striated muscle. The positive evidence consists in the demonstration that lactic acid, even in dilutions comparable to the amounts that can be formed in living muscle, can produce a similar or identical waxy transformation of the striated muscle fibers, both in vitro and in vivo; and also the observation that muscles stimulated to exhaustion, under which condition lactic acid is known to accumulate in the muscle, show microscopically changes identical with those of Zenker's waxy degeneration.
Pirfenidone in idiopathic pulmonary fibrosis - description of a German cohort
Authors: Martin J. Kohlhaeufl, Hermann Ingerl, Margit Bachnik
Journal: European Respiratory Journal (2014)

Idiopathic Pulmonary Fibrosis (IPF) is a progressive and invariably deadly disease with a prognosis similar to that of many common malignancies. Until recently, there was no drug specifically licensed for the treatment of IPF. Pirfenidone was approved in the EU and Canada for the treatment of adults with mild to moderate IPF in 2011. Pirfenidone significantly reduces disease progression as compared to placebo (Noble PW, et al. Lancet 2011;377:1760-1769), but side effects may lead to compliance problems and/or discontinuation of treatment. In spite of this, 80% of patients stay on treatment, and side effects are usually reversible, treatable, and decrease over time (Valeyre D, et al. Eur Resp J 2012; 40 (Suppl 56):563s).  This is a prospective observational single-centre cohort study at a pneumological referral centre. The target is to collect real world clinical data of Pirfenidone in 31 IPF patients for a period of about 2 years. The patients are being examined at regular intervals, and according to routine clinical practice the examinations include lung function tests, radiological imaging and blood tests, as well as assessment of possible side effects. At baseline, the mean age was 69 years, with 28 male and 3 female patients; 20 of the patients were former smokers, 11 were non-smokers, 21 needed supplemental oxygen, and HRCT data were available for 24; mean FEV1.0 was 2,3 L, mean FVC was 2.7 L; the median time since IPF diagnosis was 2 years.  The data presented cover a period from May 2012 (first patient in) until mid-2014. So far, Pirfenidone showed a favourable benefit/risk ratio in the majority of patients in this cohort.
Global epidemiology of yaws: a systematic review
Authors: Oriol Mitjà, Michael Marks, Diby J P Konan, Gilbert Ayelo, Camila Gonzalez-Beiras, Bernard Boua, Wendy Houinei, Yiragnima Kobara, Earnest N Tabah, Agana Nsiire, Damas Obvala, Fasiah Taleo, Rita Djupuri, Zhang Zaixing, Jürg Utzinger, Lasse S Vestergaard, Quique Bassat, Kingsley Asiedu
Journal: The Lancet Global Health (2015)

To achieve yaws eradication, the use of the new WHO strategy of initial mass treatment with azithromycin and surveillance twice a year needs to be extended everywhere the disease occurs. However, the geographic scope of the disease is unknown. We aimed to synthesise published and unpublished work to update the reported number of people with yaws at national and subnational levels and to estimate at-risk populations.
Do patients with older-onset rheumatoid arthritis receive less aggressive treatment?
Authors: Z Tutuncu, G Reed, J Kremer, A Kavanaugh
Journal: Annals of the Rheumatic Diseases (2006)

Rheumatoid arthritis among elderly people is an increasingly important health concern. Despite several cross-sectional studies, it has not been clearly established whether there are important clinical differences between elderly-onset rheumatoid arthritis (EORA) and younger-onset rheumatoid arthritis (YORA). The aim of this study was to compare disease activity and treatment in EORA and YORA, using the Consortium of Rheumatology Researchers of North America (CORRONA) registry, a database generated by rheumatologist investigators across the USA. From the CORRONA registry database of 9381 patients with rheumatoid arthritis, 2101 patients with disease onset after the age of 60 years (EORA) were matched, on the basis of disease duration, with 2101 patients with disease onset between the ages of 40 and 60 years (YORA). The primary outcome measures were the proportion of patients on methotrexate, multiple disease-modifying antirheumatic drugs (DMARD) and biological agents (etanercept, infliximab, adalimumab and kineret) in each group. Disease activity and severity differed slightly between the EORA and YORA groups: Disability Index of the Health Assessment Questionnaire: 0.30 v 0.35; tender joint count: 3.7 v 4.7; swollen joint count: 5.3 v 5.2; Disease Activity Score 28: 3.8 v 3.6; patient global assessment: 29.1 v 30.9; physician global assessment: 24.9 v 26.3; patient pain assessment: 31.4 v 34.9. Regarding treatment, the use of methotrexate use was slightly more common among patients with EORA (63.9%) than among those with YORA (59.6%), although the mean methotrexate dose among the YORA group was higher than that in the EORA group. The percentage of patients with EORA who were on multiple DMARD treatment (30.9%) or on biological agents (25%) was considerably lower than that of patients with YORA (40.5% and 33.1%, respectively; p<0.0001). Toxicity related to treatment was very minimal in both groups, whereas toxicities related to methotrexate were more common in the YORA group. Patients with EORA receive biological treatment and combination DMARD treatment less frequently than those with YORA, despite identical disease duration and comparable disease severity and activity.
Role of the direct and indirect pathways for glycogen synthesis in rat liver in the postprandial state.
Authors: M T Huang, R L Veech
Journal: Journal of Clinical Investigation (1988)

The pathway for hepatic glycogen synthesis in the postprandial state was studied in meal-fed rats chronically cannulated in the portal vein. Plasma glucose concentration in the portal vein was found to be 4.50 +/- 1.01 mM (mean +/- SE; n = 3) before a meal and 11.54 +/- 0.70 mM (mean +/- SE; n = 4) after a meal in rats meal-fed a diet consisting of 100% commercial rat chow for 7 d. The hepatic-portal difference of plasma glucose concentration showed that liver released glucose in the fasted state and either extracted or released glucose after feeding depending on plasma glucose concentration in the portal vein. The concentration of portal vein glucose at which liver changes from glucose releasing to glucose uptake was 8 mM, the Km of glucokinase [E.C. 2.7.1.12]. The rate of glycogen synthesis in liver during meal-feeding was found to be approximately 1 mumol glucosyl U/g wet wt/min in rats meal-fed a 50% glucose supplemented chow diet. The relative importance of the direct vs. indirect pathway for the replenishment of hepatic glycogen was determined by the incorporation of [3-3H,U-14C]glucose into liver glycogen. Labeled glucose was injected into the portal vein at the end of meal-feeding. The ratio of 3H/14C in the glucosyl units of glycogen was found to be 83-92% of the ratio in liver free glucose six minutes after the injection, indicating that the majority of exogenous glucose incorporated into glycogen did not go through glycolysis. The percent contribution of the direct versus indirect pathway was quantitated from the difference in the relative specific activity (RSA) of [3H] and [14C]-glycogen in rats infused with [3-3H,U-14C]glucose. No significant difference was found between the RSA of [3H]glycogen and [14C]glycogen, indicating further that the pathway for glycogen synthesis in liver from exogenous glucose is from the direct pathway. Our results do not support the thesis that the majority of liver glycogen is synthesized from glucose-6-phosphate derived from gluconeogenesis. Reasons for the discrepancy between current findings and other reports supporting the indirect pathway for glycogen synthesis in the liver are discussed.
<i>CCR</i> 20th Anniversary Commentary: In the Beginning, There Was PS-341
Authors: Beverly A. Teicher, Kenneth C. Anderson
Journal: Clinical Cancer Research (2015)

Abstract Proteasome inhibitors have a 20-year history in cancer therapy. The first proteasome inhibitor, bortezomib, a breakthrough treatment for multiple myeloma, moved rapidly through development from the bench in 1994 to first FDA approval in 2003. Clinical Cancer Research has chronicled the development of proteasome inhibitors with publication of reports on bortezomib, carfilzomib, and the oral proteasome inhibitor ixazomib (MLN9708). Clin Cancer Res; 21(5); 939–41. ©2015 AACR. See related article by Teicher et al., Clin Cancer Res 1999;5(9) September 1999;2638–45
Pulmonary hypertension after transjugular intrahepatic portosystemic shunt (TIPS)
Authors: R.M.J.L. van der Heijde, J.S. Laméris, B. van den Berg, C.A. Wagenvoort, C. Hilvering, H.R. van Buuren
Journal: European Respiratory Journal (1996)

We reported the case of a patient in whom severe, and ultimately fatal, pulmonary hypertension developed 1.5 yrs after transjugular intrahepatic portosystemic shunt (TIPS). Pulmonary artery pressures were not affected by 100% oxygen, prostacyclin or nifedipine. Postmortem examinations showed pulmonary and vascular abnormalities typical of pulmonary hypertension. Pulmonary artery pressures should be measured in each patient with otherwise not readily explained dyspnoea following transjugular intrahepatic portosystemic shunt.
Asymmetrical Dimethylarginine Plasma Concentrations Are Related to Basal Nitric Oxide Release but Not Endothelium-Dependent Vasodilation of Resistance Arteries in Peritoneal Dialysis Patients
Authors: Friedrich Mittermayer, Georg Schaller, Johannes Pleiner, Andreas Vychytil, Gere Sunder-Plassmann, Walter H Hörl, Michael Wolzt
Journal: Journal of the American Society of Nephrology (2005)

Vascular dysfunction in chronic renal failure may be linked to reduced nitric oxide (NO) bioactivity and increased circulating concentrations of the endogenous NO synthase inhibitor asymmetrical dimethyl L-arginine (ADMA). The association between ADMA and basal endothelial NO release and endothelium-dependent vasodilation in resistance arteries of chronic renal failure patients is unknown. Forearm blood flow responses to the endothelium-dependent vasodilator acetylcholine, the endothelium-independent vasodilator nitroglycerine, and the endothelium-dependent vasoconstrictor N(G)-monomethyl-L-arginine (L-NMMA) were assessed in 37 peritoneal dialysis patients. L-arginine and ADMA plasma concentrations were measured by HPLC. ADMA (mean +/- SEM: 0.68 +/- 0.02 micromol/L) was associated with basal forearm blood flow (r = -0.33; P < 0.05) and L-NMMA induced vasoconstriction (r = -0.55; P < 0.0005), but not with dilator effects of acetylcholine or nitroglycerine. L-arginine (68 +/- 3 micromol/L) tended to correlate with acetylcholine-induced vasodilation (r = 0.32; P = 0.05) but was not associated with other parameters. ADMA is related to basal but not to acetylcholine-stimulated NO bioactivity in patients on peritoneal dialysis. Impaired endothelium-dependent vasodilation found in chronic renal failure is not explained by elevated circulating NO synthase inhibitors in renal failure.