tbuckley/cabot-search huggingface dataset:
Association of a Decreased Number of d(CA) Repeats in the Matrix Metalloproteinase-9 Promoter with Glomerulosclerosis Susceptibility in Mice
Authors: Alessia Fornoni, Yingcai Wang, Oliver Lenz, Liliane J. Striker, Gary E. Striker
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The genetic background plays an important role in the development of progressive glomerulosclerosis. However, no marker is available for the reliable prediction of genetic susceptibility to glomerulosclerosis. Because matrix metalloproteinase-9 (MMP-9) levels are decreased in models of glomerulosclerosis and MMP-9 promoter polymorphism has been observed among patients with diabetic nephropathy, MMP-9 could be one such marker. The object of this study was to determine whether MMP-9 promoter polymorphism was associated with altered MMP-9 expression in mesangial cells (MC) from two mouse strains, i.e., ROP (glomerulosclerosis prone) and B6SJL (glomerulosclerosis resistant). ROP MC expressed 12-fold less MMP-9 mRNA. The MMP-9 promoter in ROP MC contained fewer d(CA) repeats, which was associated with lower MMP-9 expression and activity. Phorbol-12-myristate-13-acetate (3 to 60 ng/ml) increased MMP-9 expression in both MC types (3- to 4.5-fold), but the level in ROP MC never reached that in B6SLJ MC. Although reciprocal transfection of ROP and B6SJL MMP-9 promoter constructs into B6SJL and ROP cells revealed that the promoters were functional in both cell types, the B6SJL promoter was less responsive to phorbol-12-myristate-13-acetate stimulation when transfected into ROP MC, suggesting a role for other factors. In conclusion, the MMP-9 promoter exhibits a decreased number of d(CA) repeats in the sclerosis-prone strain. Because fewer d(CA) repeats associated with decreased MMP-9 expression in MC, it might be a genetic marker for glomerulosclerosis.
Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in patients with Crohn's disease with endoscopic recurrence: efficacy and safety results of a randomised, double-blind, double-dummy, multicentre trial
Authors: W. Reinisch, S. Angelberger, W. Petritsch, O. Shonova, M. Lukas, S. Bar-Meir, A. Teml, E. Schaeffeler, M. Schwab, K. Dilger, R. Greinwald, R. Mueller, E. F. Stange, K. R. Herrlinger
Journal: Gut (2010)

<h3>Objective</h3> The aim of the study was to compare azathioprine versus mesalazine tablets for the prevention of clinical recurrence in patients with postoperative Crohn9s disease (CD) with moderate or severe endoscopic recurrence. <h3>Methods</h3> This was a 1 year, double-blind, double-dummy, randomised study which took place in 21 gastroenterology centres in Austria, the Czech Republic, Germany and Israel. The study participants were 78 adults with CD who had undergone resection with ileocolonic anastomosis in the preceding 6–24 months without subsequent clinical recurrence and with a Crohn9s disease activity index (CDAI) score &lt;200, but with moderate or severe endoscopic recurrence. The study drugs were azathioprine 2.0–2.5 mg/kg/day or mesalazine 4 g/day over 1 year. The primary end point was therapeutic failure during 1 year, defined as a CDAI score ≥200 and an increase of ≥60 points from baseline, or study drug discontinuation due to lack of efficacy or intolerable adverse drug reaction. <h3>Results</h3> Treatment failure occurred in 22.0% (9/41) of azathioprine-treated patients and 10.8% (4/37) of mesalazine-treated patients, a difference of 11.1% (95% CI −5.0% to 27.3%, p=0.19). Clinical recurrence was significantly less frequent with azathioprine versus mesalazine (0/41 (0%) vs 4/37 (10.8%), p=0.031), whereas study drug discontinuation due to adverse drug reactions only occurred in azathioprine-treated patients (9/41 (22.0%) vs 0%, p=0.002). The proportion of patients showing ≥1 point reduction in Rutgeerts score between baseline and month 12 was 63.3% (19/30) and 34.4% (11/32) in the azathioprine and mesalazine groups, respectively (p=0.023). <h3>Conclusions</h3> In this population of patients with postoperative CD at high risk of clinical recurrence, superiority for azathioprine versus mesalazine could not be demonstrated for therapeutic failure. <h3>Clinical trial registration number</h3> NCT00946946.
As Space Program Approaches 21st Century, Medicine Plays Key Role
Authors: Jeanette Smith
Journal: JAMA (1990)

ALTHOUGH FUTURE physicians might find locum tenens opportunities on Mars, some of today's physician-astronauts are researching the physiologic consequences of the long-term space travel required to reach the Red Planet in the first place. Ten physician-astronauts, including 4 women, are enrolled in the National Aeronautics and Space Administration (NASA) space program. Nine have already flown on space missions and the other expects to do so in the near future. An unprecedented three physicians will be on board this year's Spacelab Life Sciences 1 (SLS-1) mission. (And two physician-astronauts, Manley L. Carter, Jr, MD, and F. Story Musgrave, MD, flew on a Department of Defense space shuttle mission in November.) The SLS-1 mission is scheduled for August 16. Among the crew members will be astronauts M. Rhea Seddon, MD, and James P. Bagian, MD, and payload specialist Francis Andrew (Drew) Gaffney, MD. This mission, involving the first space laboratory dedicated to
Interstitial insulin concentrations determine glucose uptake rates but not insulin resistance in lean and obese men.
Authors: C Castillo, C Bogardus, R Bergman, P Thuillez, S Lillioja
Journal: Journal of Clinical Investigation (1994)

Insulin action and obesity are both correlated with the density of muscle capillary supply in humans. Since the altered muscle anatomy in the obese might affect interstitial insulin concentrations and reduce insulin action, we have cannulated peripheral lymphatic vessels in lean and obese males, and compared peripheral lymph insulin concentrations with whole body glucose uptake during a euglycemic, hyperinsulinemic clamp. Lymph insulin concentrations in the lower limb averaged only 34% of arterial insulin concentrations during 150 min of insulin infusion. Obese subjects had the highest arterial (P < or = 0.0001) and lymph insulin (P < 0.005) concentrations, but the lowest glucose uptake rates (P < 0.002). In contrast to the initial steep rise then plateau of arterial insulins, both lymph insulin and whole body glucose uptake rates rose slowly and did not consistently reach a plateau. In each individual, the glucose uptake closely correlated with peripheral lymphatic insulin concentrations (mean r2 = 0.95). The coupling between glucose uptake and lymph insulin (glucose uptake/pmol insulin) was much steeper in lean subjects than in the obese (P < or = 0.0001). These results indicate that even if insulin diffusion into tissues is rate limiting for insulin action, a tissue defect rather than an insulin diffusion defect causes insulin resistance in obese subjects.
Update in Rheumatology: Evidence Published in 2012
Authors: Atul Deodhar
Journal: Annals of Internal Medicine (2013)

Updates18 June 2013Update in Rheumatology: Evidence Published in 2012Atul Deodhar, MDAtul Deodhar, MDFrom Oregon Health & Science University, Portland, Oregon.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-158-12-201306180-00107 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This update in rheumatology highlights important and promising findings published in 2012 that should affect practice or lead to larger-scale trials. Progress included new treatment recommendations for osteoarthritis and gout, approval of a new drug class to treat rheumatoid arthritis (RA), identification of a novel treatment for hepatitis C–related cryoglobulinemic vasculitis, and investigation of a biomarker that could distinguish infection from disease flare in autoimmune disease.Drug Treatment of Rheumatologic DiseaseTofacitinib Is Effective for Treatment of RA Fleischmann R ...Reference1. Schjerning Olsen AM, Fosbøl EL, Lindhardsen J, Folke F, Charlot M, Selmer C, et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: a nationwide cohort study. Circulation. 2011;123:2226-35. [PMID: 21555710] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Oregon Health & Science University, Portland, Oregon.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-0233.Corresponding Author: Atul Deodhar, MD, Division of Arthritis & Rheumatic Diseases (OP09), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239; e-mail, [email protected]edu.Author Contributions: Conception and design: A. Deodhar.Analysis and interpretation of the data: A. Deodhar.Drafting of the article: A. Deodhar.Critical revision of the article for important intellectual content: A. Deodhar.Final approval of the article: A. Deodhar.Statistical expertise: A. Deodhar.Administrative, technical, or logistic support: A. Deodhar.Collection and assembly of data: A. Deodhar.This article was published at www.annals.org on 11 April 2013. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 June 2013Volume 158, Issue 12Page: 903-906KeywordsArthritisAutoimmune diseasesDrugsGoutInfectious diseasesNSAIDsOsteoarthritisRheumatologyVasculitis ePublished: 18 June 2013 Issue Published: 18 June 2013 CopyrightCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Association of medication beliefs and self-efficacy with adherence in urban Hispanic and African–American rheumatoid arthritis patients
Authors: Tanya M Spruill, Gbenga Ogedegbe, Leslie R Harrold, Jeffrey Potter, Jose U Scher, Pamela B Rosenthal, Jeffrey D Greenberg
Journal: Annals of the Rheumatic Diseases (2013)

Adherence to rheumatoid arthritis (RA) medications varies widely but is frequently suboptimal1 and is particularly poor among racial/ethnic minority patients,2 which may help to explain the growing evidence of disparities in RA clinical outcomes.2 Beliefs about medications and self-efficacy perceptions (ie, confidence) regarding medication-taking behaviour are two modifiable patient factors that have been associated with adherence to RA medications in largely Caucasian study samples.1 Minority RA patients report more negative medication beliefs and lower self-efficacy compared with Caucasians,3–⇓5 but to our knowledge, the relationship between these psychological factors and medication adherence in these groups has not been reported.

We addressed this question in a cross-sectional study of 56 urban Hispanic and African–American RA patients recruited consecutively from the waiting rooms of two NYU-affiliated rheumatology clinics in New York City (Bellevue Hospital and Hospital for Joint Diseases) between November 2012 and January 2013. All …
Maternal Metabolic Control and Risk of Microcephaly Among Infants of Diabetic Mothers
Authors: Michael F Greene, Elizabeth N Allred, Alan Leviton
Journal: Diabetes Care (1995)

OBJECTIVE To measure the incidence of microcephaly among infants of diabetic mothers (IDM) and assess its relationship to metabolic control during pregnancy. RESEARCH DESIGN AND METHODS Head circumference data for 556 consecutive live-born singleton infants of women with insulin-requiring diabetes antedating pregnancy delivered between 28 and 40 weeks of gestation and the results of 3,242 HbA1 determinations collected during their pregnancies were examined. RESULTS There were fewer head circumferences at or below the 3rd percentne and more at or above the 97th percentik than expected. Head circumference was not related to maternal metabolic control as documented by the HbA1 values. CONCLUSIONS The less-than-expected incidence of microcephaly observed in this patient population probably reflects the well-known tendency of IDM toward macrosomia.
Robot-assisted Sacrocolpopexy for Pelvic Organ Prolapse: Surgical Technique and Outcomes at a Single High-volume Institution
Authors: Achilles Ploumidis, Anne-Françoise Spinoit, Geert De Naeyer, Peter Schatteman, Melanie Gan, Vincenzo Ficarra, Alessandro Volpe, Alexandre Mottrie
Journal: European Urology (2013)
Cost-Effectiveness of Two Screening Programs for Microalbuminuria in Type 2 Diabetes
Authors: Giuseppe Lepore, Maria Lucilla Maglio, Italo Nosari, Alessandro Roberto Dodesini, Roberto Trevisan
Journal: Diabetes Care (2002)

The presence of microalbuminuria is associated with an increased risk for developing nephropathy and cardiovascular diseases in both type 1 and type 2 diabetes (1,2,3). A proper pharmacological treatment can reduce urinary albumin excretion rate (AER) and prevent clinical nephropathy. Consequently, the screening for microalbuminuria should be an essential tool of the care for diabetic patients.

Controversy still exists regarding the type of urine specimen to be used to evaluate microalbuminuria. AER determined in timed urine collections (24 h or overnight) is the most direct measure of urinary albumin excretion (4,5). However, due to the demand of the protocol and frequent imperfect patient adherence, the AER is not practical for epidemiological studies or clinical settings. For these reasons, the measurement of the albumin-to-creatinine ratio (ACR) in a random spot urine has became a widely accepted clinical tool for assessing urinary albumin excretion (6,7,8). Recently, several semiquantitative office tests for detecting abnormal albuminuria have been developed (9).

The aim of our study was to identify the easiest and most cost-effective screening program for microalbuminuria in an outpatient clinic. We evaluated specificity, sensitivity, and positive (PPV) and negative (NPV) predictive values …
Helping people to stop smoking: the new smoking cessation guidelines
Authors: J BRITTON, A J KNOX
Journal: Thorax (1999)

Cigarette smoking is probably the most damaging of all voluntary human behaviour. Half of all smokers die prematurely as a consequence of their own smoking,1 and in 1995 in the UK alone smoking accounted for over 120 000 deaths, of which about 65 000 were due to respiratory disease.2 In addition to the harm caused to smokers themselves, passive exposure of other adults to cigarette smoke is associated with increased respiratory morbidity3 and an increased risk of lung cancer and heart disease,4 5 whilst children brought up by parents who smoke are more likely to experience lower respiratory illness in infancy,6 sudden infant death,7and middle ear disease, wheezy bronchitis and exacerbation of asthma in childhood.8-10 In addition to these direct effects of tobacco smoke, cigarette smoking affects health indirectly through the cost to the individual of sustaining their smoking habit, which contributes to financial hardship and consequent deprivation of smokers and their dependents. The total social, economic, and health related cost to society of smoking is enormous, and prevention of smoking therefore deserves to …
Comparison of isokinetic strength and H:Q ratio between ACL reconstructed athletes and non-injured athletes
Authors: Ebrahim Khosravi, Gholamali Ghasemi, Vahid Zolaktaf
Journal: British Journal of Sports Medicine (2010)

Evaluation of muscle function can be helpful in rehabilitation programmes with knee injuries. The purpose of this study was to compare isokinetic strength and H:Q ratio between ACL reconstructed (injured group) and healthy (control group) athletes. Twelve elite athletes (6 handball, 6 soccer) with a unilateral ACL rupture who had received a hamstring tendon autografts ACL reconstruction (mean duration 21 months after ACL reconstruction) were matched by motor dominance (all ACL reconstructed knees were non-dominant limbs) and sport to 12 healthy elite athletes. Each subject was tested for concentric quadriceps and hamstring peak torque, the ratio of peak torque to body weight and reciprocal muscle group ratios on a Biodex System 3 Dynamometer at 60 and 180°/s. Analyses of variance were used for data analysis. There were no significant differences in peak torque to body weight ratios and H:Q ratios between the two groups and also between their legs in both speeds (p &lt; 0.05). The ACL-reconstructed group had greater hamstring to quadriceps strength ratios in dominant and non-dominant limbs than those of the control group at both speeds but this difference was not significant. The reconstructed limbs of injured group had a significantly lower (p &lt; 0.05) quadriceps peak torque than dominant limbs of non-injured group at 60°/s. There were no significant difference in peak torque between involved knee extensor and flexor and uninvolved knee of injured group at both speeds.
GRP78 is a novel receptor initiating endothelial barrier protective response to oxidized phospholipids
Authors: Konstantin Birukov, Patrick Singleton, Tamara Mirzapoiazova, Tinghuai Wu
Journal: European Respiratory Journal (2014)

Vascular integrity or the maintenance of blood vessel continuity is a fundamental process maintained through endothelial cell-cell junctions. Defects in endothelial barrier function are an initiating factor in several disease processes including atherosclerosis, ischemia/reperfusion, tumor angiogenesis, cancer metastasis, diabetes, sepsis and acute lung injury. Therefore, understanding the mechanisms of endothelial barrier enhancement can provide novel therapeutic strategies. We have previously reported that oxidized phospholipids promote endothelial cell (EC) barrier enhancement both  in vitro  and  in vivo . In this study, we examined the initiating mechanistic events triggered by oxidized phospholipids (OxPAPC) to increase vascular integrity. Our novel data indicate that OxPAPC directly binds to the cell membrane localized chaperone protein, GRP78, associated with its cofactor, HTJ1. We found that plasma membrane localization of GRP78 is essential for trafficking of the barrier protective sphingosine 1-phosphate receptor 1 (S1P-R1) to caveolin-enriched microdomains (CEM) and consequent activation of S1P-R1, Src and Fyn tyrosine kinases and recruitment of Rac1 to CEM, processes essential for actin cytoskeletal reorganization and EC barrier enhancement. Using an animal model of acute lung injury with vascular hyper-permeability, we observed that vascular silencing of HTJ blocked OxPAPC protection from ventilator-induced lung injury and vascular leak. Our data demonstrate an essential role of GRP78 and HTJ as a  bona fide  receptor complex triggering the OxPAPC-mediated CEM dynamics and enhancement of vascular integrity.   Sources of funding:  HL076259, HL087823.
Thrombin Activates the Hypoxia-Inducible Factor-1 Signaling Pathway in Vascular Smooth Muscle Cells
Authors: A. Görlach, I. Diebold, V. B. Schini-Kerth, U. Berchner-Pfannschmidt, U. Roth, R. P. Brandes, T. Kietzmann, R. Busse
Journal: Circulation Research (2001)

Abstract —The heterodimeric transcription factor hypoxia-inducible factor-1 (HIF-1) is activated under hypoxic conditions, resulting in the upregulation of its target genes plasminogen activator inhibitor-1 (PAI-1) and vascular endothelial growth factor (VEGF). PAI-1 and VEGF are also induced in response to vascular injury, which is characterized by the activation of platelets and the coagulation cascade as well as the generation of reactive oxygen species (ROS). However, it is not known whether HIF-1 is also stimulated by thrombotic factors. We investigated the role of thrombin, platelet-associated growth factors, and ROS derived from the p22 phox -containing NADPH oxidase in the activation of HIF-1 and the induction of its target genes PAI-1 and VEGF in human vascular smooth muscle cells (VSMCs). Thrombin, platelet-derived growth factor-AB (PDGF-AB), and transforming growth factor-β 1 (TGF-β 1 ) upregulated HIF-1α protein in cultured and native VSMCs. This response was accompanied by nuclear accumulation of HIF-1α as well as by increased HIF-1 DNA-binding and reporter gene activity. The thrombin-induced expression of HIF-1α, PAI-1, and VEGF was attenuated by antioxidant treatment as well as by transfection of p22 phox antisense oligonucleotides. Inhibition of p38 mitogen-activated protein kinase and phosphatidylinositol-3-kinase significantly decreased thrombin-induced HIF-1α, PAI-1, and VEGF expression. These findings demonstrate that the HIF-1 signaling pathway can be stimulated by thrombin and platelet-associated growth factors and that a redox-sensitive cascade activated by ROS derived from the p22 phox -containing NADPH oxidase is crucially involved in this response.
Continuous-wave Doppler echocardiographic detection of pulmonary regurgitation and its application to noninvasive estimation of pulmonary artery pressure.
Authors: T Masuyama, K Kodama, A Kitabatake, H Sato, S Nanto, M Inoue
Journal: Circulation (1986)

Continuous-wave Doppler echocardiography was used to estimate pulmonary artery pressures by measuring pulmonary regurgitant flow velocity in 21 patients with pulmonary hypertension (mean pulmonary artery pressure greater than or equal to 20 mm Hg) and 24 patients without pulmonary hypertension. The pulmonary regurgitant flow velocity patterns, characterized by a rapid rise in flow velocity immediately after closure of the pulmonary valve and a gradual deceleration until the next pulmonary valve opening, were successfully obtained in 18 of the 21 patients with pulmonary hypertension and in 13 of the 24 patients without pulmonary hypertension. As pulmonary artery pressure increased, pulmonary regurgitant flow velocity became higher; the pulmonary artery-to-right ventricular pressure gradient in diastole (PG) was estimated from the pulmonary regurgitant flow velocity (V) by means of the simplified Bernoulli equation (PG = 4V2). The Doppler-determined pressure gradient at end-diastole correlated well with the catheter measurement of the pressure gradient at end-diastole (r = .94, SEE = 3 mm Hg) and with pulmonary artery end-diastolic pressure (r = .92, SEE = 4 mm Hg). The peak of Doppler-determined pressure gradient during diastole correlated well with mean pulmonary artery pressure (r = .92, SEE = 5 mm Hg). Thus continuous-wave Doppler echocardiography was useful for noninvasive estimation of pulmonary artery pressures.
Modified sleep apnea clinical score: Is usefull in our clinical practice?
Authors: M. Isabel Andrade, José Antonio Cascante, Amaia Iridoy, María Hernández, Pilar Cebollero, V. Manuel Eguía, José Javier Hueto
Journal: European Respiratory Journal (2011)

Introduction:  The aim of our work was to determine if the corrected neck perimeter (CNP) is useful in the OSAS severity prediction.   Methods:  Descriptive study in which we have included 337 patients sent to the sleep unit by OSAS9s clinical suspicion, from January 2007-2011 whom a polisomnografy was realized. We calculated the CNP according to Flemong9s formula, which adds 3cm to the measured neck perimeter if the individual is a snorer, other 3cm if they have episodes of choke or gasp most nights and 4cm if they are hypertense. There have not been included in this study the patients in whom we couldn9t calculate the formula. We have considered 3 degrees of severity: 1 if the CNP is  48 cm. We consider a mild OSAS if the IAH is 5-15, moderate if it is between 15-30, and severe if IAH>30.   Results:  The middle age of our patients was 50y (16-80); 78% males. The patient9s percentage with different degrees of OSAS9s severity according to his CNP is expressed in the table.  IAH9s average was 24 in the group with CNP  48, it was 42, being statistically significant difference (p   Conclusions:  The CNP is significantly correlated by the OSAS severity. By contrast in others studies, in our environment, the IAH> 5 probability post test, is 72%, when the CNP is > 43, and doesn9t predict severity. The IAH> 5 probability post test is 96% if the CPN is> 48 and predicts OSAS severity.