tbuckley/cabot-search huggingface dataset:
Repair of joint erosions in rheumatoid arthritis: prevalence and patient characteristics in a large inception cohort
Authors: M. P. M. van der Linden, R. Boja, N. B. Klarenbeek, T. W. J. Huizinga, D. M. van der Heijde, A. H. M. van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2009)

Joint destruction in rheumatoid arthritis (RA) was until recently seen as an irreversible state. Lately, it was found that repair of bone erosions occurs; however, little is known about its prevalence.To investigate the frequency of repair and patients' characteristics associated with repair in an inception cohort.250 patients with RA, included in the Leiden Early Arthritis Clinic between 1993 and 2000 and treated with conventional disease-modifying antirheumatic drugs, were studied (mean follow-up 10.1 years). Radiographs obtained annually were scored using the Sharp-van der Heijde method, initially aware of the chronology. Patients with a negative change in erosion scores on subsequent radiographs were selected and their series of radiographs were re-scored with concealed time sequence by three readers. Repair was defined as agreement between two readers of a negative change in erosion scores that persisted for at least 2 years.Repair was identified in 32 joints in 18 patients (7.2%). Patients with repair had a greater prevalence of autoantibodies (rheumatoid arthritis, anti-citrullinated protein antibody) and a higher level of joint destruction. In the joints with repair, arthritis was absent in the 2 years preceding repair.Repair occurred in 7.2% of the patients with RA, particularly in clinically inactive joints in patients with severe destructive disease.
Effect of bipolar androgen therapy for asymptomatic men with castration-resistant prostate cancer: Results from a pilot clinical study
Authors: Michael T. Schweizer, Emmanuel S. Antonarakis, Hao Wang, A. Seun Ajiboye, Avery Spitz, Haiyi Cao, Jun Luo, Michael C. Haffner, Srinivasan Yegnasubramanian, Michael A. Carducci, Mario A. Eisenberger, John T. Isaacs, Samuel R. Denmeade
Journal: Science Translational Medicine (2015)

Intermittent treatment with high-dose testosterone shows therapeutic potential in patients with castration-resistant prostate cancer.
Recurrent adult respiratory distress-like syndrome associated with propylthiouracil therapy
Authors: JC Chevrolet, G Guelpa, JA Schifferli
Journal: European Respiratory Journal (1991)

We report a patient who presented with an association between propylthiouracil treatment and recurrent episodes of an adult respiratory distress-like syndrome (ARDS). The bouts of ARDS were associated with a generalized reaction suggestive of systemic lupus erythematosus (SLE), responsive to corticosteroid therapy.
Hypertensive Renal Damage in Metabolic Syndrome Is Associated with Glucose Metabolism Disturbances
Authors: Julia[Combining Acute Accent]n Segura, Carlos Campo, Cecilia Rolda[Combining Acute Accent]n, Helle Christiansen, Luis Vigil, Rafael Garci[Combining Acute Accent]a-Robles, Jose[Combining Acute Accent] L. Rodicio, Luis M. Ruilope
Journal: Journal of the American Society of Nephrology (2004)

Recent evidence highlights the relationship between metabolic syndrome (MS) and increased risk of cardiovascular (CV) diseases. Mild renal function abnormalities are associated with an enhanced CV risk, considered to be due to the presence of associated risk factors. Hence, MS and renal abnormalities could be linked and contribute to augment CV risk. For estimating the prevalence of diminished creatinine clearance (CC; <60 ml/min per 1.73 m(2)) in hypertensive patients with or without MS and for investigating the factors accompanying this abnormality, 1625 hypertensive patients, aged 18 yr or older, were included. The presence of MS was defined according to the Adult Treatment Panel III criteria. The overall prevalence of MS was 49.4% (n = 802). No significant difference was found for CC between those with and without MS, albeit the presence of MS was accompanied by greater urinary albumin excretion (P = 0.01). The prevalence of a diminished CC was also similar in the two groups. MS-positive patients presented a progressive decay in CC when classified as normoglycemic (n = 319), impaired fasting glucose (n = 237), and diabetic patients (n = 246; 85.9 +/- 30.2, 81.8 +/- 26.8, and 75.2 +/- 25.7 ml/min per 1.73 m(2), respectively; P = 0.0007 linearity test) and the opposite for microalbuminuria (29.5 +/- 45.5, 45.0 +/- 96.6, and 74.1 +/- 146.3 mg/24 h, respectively; P = 0.001 linearity test). In multiple regression analysis, factors related to the finding of a diminished CC in MS and non-MS patients were similar. Hypertensive patients at a relatively young age present with an elevated prevalence of minor abnormalities of renal function that is mostly related to the presence of metabolic alteration of glucose together with age and BP.
Global down-regulation of HOX gene expression in PML-RARα+ acute promyelocytic leukemia identified by small-array real-time PCR
Authors: Alexander Thompson, Michael F. Quinn, David Grimwade, Claire M. O'Neill, Momin R. Ahmed, Sean Grimes, Mary Frances McMullin, Finbarr Cotter, Terence R. J. Lappin
Journal: Blood (2003)
Organisation of health care during an outbreak of Marburg haemorrhagic fever in the Democratic Republic of Congo, 1999
Authors: Robert Colebunders, Hilde Sleurs, Patricia Pirard, Matthias Borchert, Modeste Libande, Jean Pierre Mustin, Antoine Tshomba, LÃ©on Kinuani, Loku Abisa Olinda, Florimond Tshioko, Jean-Jacques Muyembe-Tamfum
Journal: Journal of Infection (2003)
Palpating muscles, massaging the evidence? An editorial relating to 'Terminology and classification of muscle injuries in sport: The Munich consensus statement'
Authors: Johannes L Tol, Bruce Hamilton, Thomas M Best
Journal: British Journal of Sports Medicine (2012)

There is no denying the fact that appropriate classification of muscle injuries is a major challenge for both clinicians and researchers. The classification system proposed in this issue has been developed by highly experienced clinicians, and has the potential to impact upon both our daily practice and future research.1

Although the proposed classification of muscle injuries may reflect the daily practice of many physicians, it will likely challenge the practice and mindset of others. Notably, this classification system is broadly inclusive of various forms of muscle-related pain, and reaffirms the central role of history taking and physical examination in the diagnosis of muscle injuries and in predicting their subsequent clinical trajectory. The emphasis on clinical assessment contrasts with manuscripts in recent years which have prioritised the use of imaging as a key diagnostic determinant—at the expense of clinical assessment.2 ,3 The authors are therefore to be commended.

The proposed classification, perhaps more than any other classification, highlights the paucity of evidence from which to develop classifications. We lack high-level studies to confidently guide clinical management of muscle injuries. As a result of both the poor state of evidence and the complexity of the challenge, this proposed classification of muscle injuries raises as many questions as solutions and, thus, it has the potential to promote urgently needed research in this area.

When determining an athlete's prognosis after muscle injury, the only consistently reported (level II) evidence suggests that ‘MRI-negative’ muscle injuries have a better prognosis than injuries which are evident on MRI (MRI-positive).4–7 Several studies have provided convincing evidence that ‘MRI-negative’ (without increased signal intensity) predicts a favourable outcome and a quick return to sports.4–7 For example, Ekstrand …
Response to Letter Regarding Article, “Mortality and Sudden Death in Pediatric Left Ventricular Noncompaction in a Tertiary Referral Center”
Authors: Jeffrey J. Kim, Samuel T. Brescia, Joseph W. Rossano, Ricardo Pignatelli, John L. Jefferies, Jack F. Price, Jamie A. Decker, Susan W. Denfield, W. Jeffrey Dreyer, O’Brian Smith, Jeffrey A. Towbin
Journal: Circulation (2014)
Outcomes of Nonsevere Relapses in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis Treated With Glucocorticoids
Authors: E. M. Miloslavsky, U. Specks, P. A. Merkel, P. Seo, R. Spiera, C. A. Langford, G. S. Hoffman, C. G. M. Kallenberg, E. W. St.Clair, N. K. Tchao, L. Ding, D. Iklé, M. Villareal, N. Lim, P. Brunetta, F. C. Fervenza, P. A. Monach, J. H. Stone
Journal: Arthritis & Rheumatology (2015)

Nonsevere relapses are more common than severe relapses in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but their clinical course and treatment outcomes remain largely unexamined. We undertook this study to analyze the outcomes of patients with nonsevere relapses in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial who were treated with prednisone according to a prespecified protocol.RAVE was a randomized, double-blind, placebo-controlled trial comparing rituximab (RTX) to cyclophosphamide (CYC) followed by azathioprine (AZA) for induction of remission. Patients who experienced nonsevere relapses between months 1 and 18 were treated with a prednisone increase without a concomitant change in their nonglucocorticoid immunosuppressants, followed by a taper.Forty-four patients with a first nonsevere relapse were analyzed. In comparison to the 71 patients who maintained relapse-free remission over 18 months, these patients were more likely to have proteinase 3-ANCAs, diagnoses of granulomatosis with polyangiitis (Wegener's), and a history of relapsing disease at baseline. A prednisone increase led to remission in 35 patients (80%). However, only 13 patients (30%) were able to maintain second remissions through the followup period (mean 12.5 months); 31 patients (70%) had a second disease relapse, 14 of them with severe disease. The mean time to second relapse was 9.4 months (4.7 months in the group treated with RTX versus 13.7 months in the group treated with CYC/AZA; P < 0.01). Patients who experienced nonsevere relapses received more glucocorticoids than those who maintained remission (6.7 grams versus 3.8 grams; P < 0.01).Treatment of nonsevere relapses in AAV with an increase in glucocorticoids is effective in restoring temporary remission in the majority of patients, but recurrent relapses within a relatively short interval remain common. Alternative treatment approaches are needed for this important subset of patients.
Hyperlipidaemia in hyperuricaemia and gout
Authors: B. EMMERSON
Journal: Annals of the Rheumatic Diseases (1998)

The finding of hyperlipidaemia in patients with hyperuricaemia and gout is common. The usual abnormality is hypertriglyceridaemia (type IV hyperlipoproteinaemia),1 2 being reported in between 25% and 60% of patients with gout.3 4 This finding has been related to reports of an increased frequency of coronary artery disease in some patients with gout and has contributed to the suggestion that the urate concentration might be an indicator of coronary risk. Now that gouty arthritis itself is so treatable, an associated disorder that might reduce the life span becomes even more important in the management of a patient with gout.

However, our understanding of the mechanism of any association between hypertriglyceridaemia and hyperuricaemia is far from complete and this becomes increasingly important when determining the factors that contribute to the development of hyperuricaemia and gout in a particular person. No longer can it be assumed that there is a common aetiology for the hyperuricaemia in patients who present with an acute urate crystal arthropathy and refer to it as “primary gout”. Similarly, it is no longer expected that each patient with gout would have inherited a “gouty diathesis”, unless you regard this concept as meaning a relatively poor renal clearance of urate in the presence of otherwise normal renal function.5 Hyperuricaemia in most patients is found to have multiple causes, some genetic and others environmental, with many of the latter being able to be modified, potentially correcting the contribution of that cause to the hyperuricaemia.6 7 

In such an assessment, the …
MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy
Authors: Julie Halkein, Sebastien P. Tabruyn, Melanie Ricke-Hoch, Arash Haghikia, Ngoc-Quynh-Nhu Nguyen, Michaela Scherr, Karolien Castermans, Ludovic Malvaux, Vincent Lambert, Marc Thiry, Karen Sliwa, Agnes Noel, Joseph A. Martial, Denise Hilfiker-Kleiner, Ingrid Struman
Journal: Journal of Clinical Investigation (2013)

Peripartum cardiomyopathy (PPCM) is a life-threatening pregnancy-associated cardiomyopathy in previously healthy women. Although PPCM is driven in part by the 16-kDa N-terminal prolactin fragment (16K PRL), the underlying molecular mechanisms are poorly understood. We found that 16K PRL induced microRNA-146a (miR-146a) expression in ECs, which attenuated angiogenesis through downregulation of NRAS. 16K PRL stimulated the release of miR-146a-loaded exosomes from ECs. The exosomes were absorbed by cardiomyocytes, increasing miR-146a levels, which resulted in a subsequent decrease in metabolic activity and decreased expression of Erbb4, Notch1, and Irak1. Mice with cardiomyocyte-restricted Stat3 knockout (CKO mice) exhibited a PPCM-like phenotype and displayed increased cardiac miR-146a expression with coincident downregulation of Erbb4, Nras, Notch1, and Irak1. Blocking miR-146a with locked nucleic acids or antago-miRs attenuated PPCM in CKO mice without interrupting full-length prolactin signaling, as indicated by normal nursing activities. Finally, miR-146a was elevated in the plasma and hearts of PPCM patients, but not in patients with dilated cardiomyopathy. These results demonstrate that miR-146a is a downstream-mediator of 16K PRL that could potentially serve as a biomarker and therapeutic target for PPCM.
Raised serum immunoglobulin E in Wegener's granulomatosis.
Authors: D.L Conn, G.J Gleich, R.A DeRemee, T.J McDonald
Journal: Annals of the Rheumatic Diseases (1976)

Five patients with Wegner's granulomatosis were found to have significantly raised serum immunoglobulin E (IgE) levels. The rise in IgE was not related to the extent of clinical involvement, was not part of a generalized serum immunoglobulin rise, and was not associated with eosinophilia. Raised serum IgE may be a clue to the pathogenesis of this disease.
A Constitutively Active Dioxin/Aryl Hydrocarbon Receptor Promotes Hepatocarcinogenesis in Mice
Authors: Oliver Moennikes, Sandra Loeppen, Albrecht Buchmann, Patrik Andersson, Carina Ittrich, Lorenz Poellinger, Michael Schwarz
Journal: Cancer Research (2004)

Abstract The dioxin/aryl hydrocarbon receptor (AhR) functions as a ligand-activated transcription factor regulating transcription of a battery of genes encoding enzymes involved in drug metabolism. Known ligands include polycyclic aromatic hydrocarbons, certain polychlorinated biphenyls, and the polyhalogenated dioxins including 2,3,7,8-tetrachlorodibenzo-p-dioxin. Both polyhalogenated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin are potent promoters of rodent hepatocarcinogenesis in two-stage initiation-promotion experiments. Although several lines of evidence indicate the involvement of the AhR in toxic effects mediated by polyhalogenated biphenyls and dioxins, its involvement in tumor promotion has not been unequivocally proven. In the present study, a transgenic mouse line expressing a constitutively active AhR (CA-AhR) has been used to investigate the role of the AhR in hepatocarcinogenesis. Male AhR wild-type and CA-AhR-transgenic B6C3F1-mice were treated with a single injection of the hepatocarcinogen N-nitrosodiethylamine at 6 weeks of age and were subsequently kept untreated on control diet. Thirty five weeks after carcinogen treatment, mice were sacrificed, and the prevalence and multiplicity of liver tumors were determined. Whereas only 1 small liver tumor was observed in 15 AhR-wild-type mice, 19 tumors (two &amp;gt;1 cm in diameter) were present in 18 CA-AhR-transgenic mice. This result demonstrates the oncogenic potential of the activated AhR and implicates an important role of the receptor in promotion of hepatocarcinogenesis. A microarray-based gene expression-profiling analysis revealed down-regulation in the liver of CA-AhR-transgenic mice of a cluster of genes encoding heat shock proteins, including GRP78/BiP, Herp1, Hsp90, DnaJ (Hsp40) homologue B1, and Hsp105, which are important for protein folding and quality control.
Cigarette smoking and chronic liver diseases
Authors: J. Altamirano, R. Bataller
Journal: Gut (2010)

Tobacco smoking is the inhalation of smoke from burned dried or cured leaves of the tobacco plant, most often in the form of a cigarette. Cigarette smoke contains a toxic collection of more than 4000 chemicals including nicotine, which combined give rise to addictive stimulant and euphoriant properties. According to the World health Organization, about one-third of the world's male population smokes tobacco and cigarette smoking (CS) killed 100 million people worldwide in the 20th century. Therefore, CS is considered a major cause of preventable morbidity and mortality worldwide.1 2 There are three main clinical consequences of prolonged exposure to CS. First, it causes several chronic respiratory ailments, including chronic bronchitis, emphysema and lung fibrosis, and is associated with an increase in respiratory infections.3 Second, it is associated with an increased incidence of a variety of cancers including lung, oral, oesophagus, pancreas and colon.4 And third, CS increases the risk of atherothrombotic clinical events such as myocardial infarction and stroke.5 The risk of death in these patients increases with increasing exposure to cigarette smoke, measured by the number of cigarettes smoked daily, the duration of smoking, the degree of inhalation and the age of initiation. In addition, exposure to environmental tobacco smoke in non-smokers is associated with an increased risk of cardiovascular events and asthma.6 7 There is convincing evidence that smoking cessation has beneficial effects, even after a cardiovascular event.5–8 In the last decade, health authorities have made a considerable effort to promote smoking cessation. Although the prevalence of smoking has declined over the last few decades in developed countries, it is rapidly increasing in developing countries, with an emerging epidemic of tobacco-related diseases.9

Hepatologists have traditionally paid scant attention to the deleterious effects of CS.10 This reflects the fact that …
<i>PPAR</i>γ Variant Influences Angiographic Outcome and 10-Year Cardiovascular Risk in Male Symptomatic Coronary Artery Disease Patients
Authors: Jakub J. Regieli, J. Wouter Jukema, Pieter A. Doevendans, Aeilko H. Zwinderman, Yolanda van der Graaf, John J. Kastelein, Diederick E. Grobbee
Journal: Diabetes Care (2009)

Activation of peroxisome proliferator-activated receptor (PPAR)-gamma signaling influences metabolic profiles and the propensity toward inflammation. Small-molecule stimulation of PPARgamma is investigated for secondary prevention of cardiovascular disease. The common PPARgamma Pro12Ala variant has functional and prognostic consequences. A protective effect of the 12Ala-allele carriership on diabetes and myocardial infarction in healthy populations has been suggested. The relevance of this pathway also needs exploration in patients with manifest vascular disease. We investigated the effects of carriership of the Pro12Ala variant on angiographic and cardiovascular event outcomes in male patients with symptomatic coronary artery disease (CAD).The Regression Growth Evaluation Statin Study (REGRESS) cohort was genotyped for the Pro12Ala variant (rs1801282). Ten-year follow-up was derived from nation-wide registries, and risks were estimated using proportional hazards. Quantitative coronary angiography measurements were obtained and relations with genotype estimated using a generalized linear model.Genotypes ascertained (n = 679) comprised 540 (80%) Pro/Pro, 126 (19%) Pro/Ala, and 13 (2%) Ala/Ala subjects. The 12Ala allele was associated with less extensive focal (P = 0.001) and diffuse (P = 0.002) atherosclerosis and lower 10-year cardiovascular risk. Hazard ratios were 0.10 (95% CI 0.01-0.70, P = 0.02) for ischemic heart disease and 0.24 (0.08-0.74, P = 0.013) for vascular death, per each added copy of 12Ala, respectively.Carriers of the 12Ala allele of PPARgamma have less widespread CAD and are considerably protected against 10-year (cardio)vascular morbidity and mortality. These long-term findings in patients with manifest CAD support an important role of PPARgamma in determining vascular risk.
Adjuvant therapy with cetuximab for locally advanced squamous cell carcinoma of the oropharynx: results from a randomized, phase II prospective trial
Authors: R. Mesía, A. Rueda, R. Vera, A. Lozano, J.A. Medina, D. Aguiar, F. Árias, G. Triana, J. Carles, R. López-López
Journal: Annals of Oncology (2012)
The Effect of Bcrp1 (Abcg2) on the <i>In vivo</i> Pharmacokinetics and Brain Penetration of Imatinib Mesylate (Gleevec): Implications for the Use of Breast Cancer Resistance Protein and P-Glycoprotein Inhibitors to Enable the Brain Penetration of Imatinib in Patients
Authors: Pauline Breedveld, Dick Pluim, Greta Cipriani, Peter Wielinga, Olaf van Tellingen, Alfred H. Schinkel, Jan H.M. Schellens
Journal: Cancer Research (2005)

Imatinib mesylate (signal transduction inhibitor 571, Gleevec) is a potent and selective tyrosine kinase inhibitor, which was shown to effectively inhibit platelet-derived growth factor-induced glioblastoma cell growth preclinically. However, in patients, a limited penetration of imatinib into the brain has been reported. Imatinib is transported in vitro and in vivo by P-glycoprotein (P-gp; ABCB1), which thereby limits its distribution into the brain in mice. Previously, imatinib was shown to potently inhibit human breast cancer resistance protein (BCRP; ABCG2). Here, we show that imatinib is efficiently transported by mouse Bcrp1 in transfected Madin-Darby canine kidney strain II (MDCKII) monolayers. Furthermore, we show that the clearance of i.v. imatinib is significantly decreased 1.6-fold in Bcrp1 knockout mice compared with wild-type mice. At t = 2 hours, the brain penetration of i.v. imatinib was significantly 2.5-fold increased in Bcrp1 knockout mice compared with control mice. We tested the hypothesis that P-gp and BCRP inhibitors, such as elacridar and pantoprazole, improve the brain penetration of imatinib. Firstly, we showed in vitro that pantoprazole and elacridar inhibit the Bcrp1-mediated transport of imatinib in MDCKII-Bcrp1 cells. Secondly, we showed that co-administration of pantoprazole or elacridar significantly reduced the clearance of i.v. imatinib in wild-type mice by respectively 1.7-fold and 1.5-fold. Finally, in wild-type mice treated with pantoprazole or elacridar, the brain penetration of i.v. imatinib significantly increased 1.8-fold and 4.2-fold, respectively. Moreover, the brain penetration of p.o. imatinib increased 5.2-fold when pantoprazole was co-administered in wild-type mice. Our results suggest that co-administration of BCRP and P-gp inhibitors may improve delivery of imatinib to malignant gliomas.