tbuckley/cabot-search huggingface dataset:
AB0609 Costunolide inhibits rankl-induced osteoclast differentiation by suppressing rankl-mediated c-fos transcriptional activity.
Authors: C.-H. Lee, W.-H. Yoo, Y.-G. Jeong, J.-M. Oh, M.-S. Lee, S.-I. Lee, Y.-H. Cheon, H.-B. Kwak
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Costunolide, a sesquiterpene lactone, exhibits anti-inflammatory and anti-oxidant propertiesand mediates apoptosis. However, its effects and mechanism of action in osteoclasts remains unknown. <h3>Objectives</h3> We investigated the role of constunolide in RANKL-induced osteoclast differentiation. <h3>Methods</h3> Osteoclast formation was evaluated in bone marrow cells (BMC) in the presence or absence of constunolide. The expression of c-fos and NFATc1 mRNA in osteoclast precursor were assessed by RT-PCR. The levels of c-fos and NFATc1 protein were assessed by western blot. Also the MAPKs and NF-κB pathways were measured using Western blot analysis. <h3>Results</h3> we found that costunolide significantly inhibited RANKL-induced BMM differentiation into osteoclasts in a dose-dependent manner without affeting cytotoxicity. Costunolide did not regulate the early signaling pathways of RANKL, including the mitogen activated protein kinase (MAPK) and NF-κB pathways. However, costunolide suppressed nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) expression via inhibition of <i>c-Fos</i> transcriptional activity without affecting RANKL-induced <i>c-Fos</i> expression. The inhibitory effects of costunolide were rescued by overexpression of constitutively active (CA)-NFATc1. <h3>Conclusions</h3> Taken together, our results suggest that costunolide inhibited RANKL-induced osteoclast differentiation by suppressing RANKL-mediated <i>c-Fos</i> transcriptional activity. <h3>Disclosure of Interest</h3> None Declared
OC-150 A decade of change in the management of severe gastrointestinal haemorrhage
Authors: A S Dhadwal, E Platt, E Morad, A Osborne, A Watkinson, S Wajed
Journal: Gut (2012)

<h3>Introduction</h3> Acute major gastrointestinal bleeding represents a serious and complex clinical challenge requiring a multi-modality approach involving endoscopic, radiological and surgical intervention. The optimal management of this condition has evolved significantly in recent years, and this retrospective study evaluated the changing trends in practice over a 10-year period. <h3>Methods</h3> A comprehensive and retrospective analysis of all the patients treated for acute serious gastrointestinal haemorrhage (SGIH), not controllable by endoscopic therapy alone between 2001 and 2011 was performed. This time period overlaps the introduction of a dedicated 24-h interventional radiology service (2009). Baseline demographics, including Rockall and Glasgow Scores, and outcomes from interventional radiological and/or surgical intervention were analysed. <h3>Results</h3> Ninety-nine patients in the 10-year period required radiological or surgical intervention for SGIH with a median age of 70 years old (range 22–93). Sixty-seven patients (68%) were treated with surgery alone, with a successful outcome in 63 (94%), and a mortality rate of 6%. Radiological intervention was carried out in 32 patients with a successful outcome for this modality alone in 23 (72%), with one death. Eight patients underwent surgery due to incomplete radiological control, with a successful outcome in 7 (88%), but with one death, giving an overall mortality of 6%. Throughout the 10-year period, there was a sequential decline in the use of primary surgical intervention in favour of a multi-modal radiology-surgery approach. <h3>Conclusion</h3> Severe gastro-intestinal haemorrhage in the acute setting, when not amenable to successful endoscopic therapy remains a serious condition with significant mortality (6%). The introduction of interventional radiological techniques however now means that the majority of patients can be successfully managed without operative surgery, but this still plays an important role for complex or refractory patients. <h3>Competing interests</h3> None declared.
Aureomycin in the Treatment of Actinomycosis
Authors: Leon V. McVay, Frances Guthrie, Douglas H. Sprunt
Journal: New England Journal of Medicine (1951)

ALTHOUGH actinomycosis has been described for over 70 years, its frequency and potential seriousness have not been given recognition in the American literature until quite recently. The first monograph in English on this subject was not published until 1938.1 Since then, numerous articles dealing with this condition have appeared. With an increased awareness on the part of physicians and dentists, together with steadily improving diagnostic facilities, an increasing recognition of this infection is to be expected. Although much progress has been made in the treatment of actinomycosis, the mortality and morbidity are still significant. This is especially true in the . . .
A Comparison of Six Weeks with Six Months of Oral Anticoagulant Therapy after a First Episode of Venous Thromboembolism
Authors: S Schulman, A S Rhedin, P Lindmarker, A Carlsson, G Lärfars, P Nicol, E Loogna, E Svensson, B Ljungberg, H Walter
Journal: New England Journal of Medicine (1995)

The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism is still a matter of debate.
Extensively Drug-Resistant Tuberculosis
Authors: Mani Cheruvu, Satish Bhadriraju
Journal: New England Journal of Medicine (2008)

To the Editor: Mitnick and colleagues (Aug. 7 issue)1 have raised awareness about the clinical management and outcomes of extensively drugresistant tuberculosis in Peru. Although a cure rate of 60% is encouraging, we caution against generalizing these findings to other high-burden settings. Of 95 patients with extensively drug-resistant tuberculosis (of whom about 60% were negative for the human immunodeficiency virus) we identified in Cape Town, South Africa, between 2006 and 2008, only 10% underwent culture conversion, despite intensive inpatient therapy, including capreomycin-based regimens. This difference may be due to higher rates of alcohol and drug abuse, smoking, and malnutrition among our patients, along with differences in strain virulence2 and host immunity (including underlying profiles of helper T cells).3 Another factor may be our minimal use of moxifloxacin (which was administered to 72% of the patients in the study by Mitnick et al., as compared with 1% in our cohort). The clinical additive value of this agent requires further evaluation, and it would be useful to know the level of cross-resistance between the different quinolone subclasses in the Peruvian study. Thus, in an African setting, treatment outcomes for patients with extensively drug-resistant tuberculosis are poor. This underscores the importance of strengthening laboratory capacity, programs for tuberculosis treatment, and the rollout of rapid diagnostic tests.4
The Surgery of the Innominate Artery
Authors: Gustaf E. Lindskog
Journal: New England Journal of Medicine (1946)

THE first recorded operation on the innominate artery was performed by Valentine Mott of New York on May 11, 1818. Ligation of this vessel in an attempt to cure a traumatic subclavian aneurysm was followed by wound sepsis, secondary hemorrhage and death. Such was the fate of all subsequent surgical attempts in the preaseptic era until the twentieth recorded case, in which a successful ligation for subclavian aneurysm was performed on May 15, 1864, by Andrew Smyth,1 of New Orleans. This patient was younger, and Fate was kinder. Recovery ensued after a terrifying series of hemorrhages, for the treatment of . . .
Acetylation of Sulfanilamide and Para-Aminobenzoic Acid in Diabetic Patients
Authors: Yoshio Goto, Yukio Ujiie, Joji Kato, Yoshinori Sasaki
Journal: New England Journal of Medicine (1959)

CHARALAMPOUS and Hegsted1 found that metabolic acetylation is impaired in experimental diabetes. They demonstrated this in alloxan-diabetic rats by the measurement of acetylated paraaminobenzoic acid (PABA) excreted in the urine after the intraperitoneal injection of PABA. It is known that this acetylation is carried out by acetyl coenzyme A. The present study was undertaken to ascertain whether such disturbances in acetylation occur in diabetic patients. Our results showed that no clearly significant impairment of acetylation is present in diabetes mellitus, in agreement with the findings of others.2 , 3 MethodNinety-two diabetic inpatients and 156 nondiabetic patients and healthy adults served as . . .
DUAL ANTI-PLATELET THERAPY IS NOT SUPERIOR TO ASPIRIN ALONE AFTER CORONARY ARTERY BYPASS IN DIABETIC PATIENTS WITH MULTI-VESSEL DISEASE: INSIGHTS FROM THE FREEDOM TRIAL
Authors: Sean Van Diepen, Valentin Fuster, Subodh Verma, Taye H. Hamza, F. Sandra Siami, Shaun Goodman, Michael Farkouh
Journal: Journal of the American College of Cardiology (2016)
SAT0538 Cyclophosphamide Induced Bladder Toxicity and Protective Effect of 2-Mercaptoethane Sulfonate (MESNA) in Systemic Autoimmune Disorders
Authors: N. Yilmaz, H. Emmungil, G. Ozen, F. Yildiz, I. Dogan, A. Balkarlı, S. Yasar, O. N. Pamuk, Y. Cagatay, G. Cetin, K. Aksu, H. Direskeneli, E. Erken, O. Karadag, V. Cobankara, T. Kasifoglu, M. Sayarlıoglu, S. Yavuz
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> To assess bladder toxicity of Cyclophosphamide (CYC) treatment and preventive effect of 2-mercaptoethane sulfonate (Mesna) in systemic autoimmune disorders. <h3>Methods</h3> Six hundred fifty-six patients (F/M:479/177) with various systemic autoimmune disease who were treated with CYC at least 3 months were included to this analysis. The route of CYC administration, cumulative dosage and duration as well as mesna usage were evaluated. Relationship between hemorrhagic cystitis and six variables including CYC dosage route of administration, disease and mesna usage were assessed by survival analysis. <h3>Results</h3> We identified 8/656 (1.2%) patients with hemorrhagic cystitis and 2/260 (0.76%) patients with bladder cancer. The median time for diagnosis to hemorrhagic cystitis was 4 (range 3-12) months and bladder cancer was 8 (6 and 10.9) years. Two hundred fifty-one (38%) patients during IV CYC administration had received mesna. The incidence of hemorrhagic cystitis was not different between patients with and without using mesna [2/251 (0.8%) vs. 6/405 (1.4%) respectively, HR:1.04, CI 0.2-5.2, p=0.9]. Hemorrhagic cystitis was found higher in Scleroderma (SSc) patients compared to other autoimmune disease [SSc: 4/215 (1.86%), SLE: 2/227 (0.88%) and vasculitis: 2/186 (1.07%), HR: 6.4, p=0.01] and the mean CYC dose was not different between the groups(p&gt;0.05). The mean (±SEM) CYC dose was 13.1±0.52 (range 1.5-144) g, duration of CYC treatment was 15.5±0.47 (range 3-102) months and follow-up time after CYC treatment was 59.4±2.0 (range 3-365) months. Cumulative CYC dose was higher in patients with hemorrhagic cystitis without significance (38.9±42.6 vs. 12.7±11.9 gram respectively, p=0.058). The mean cumulative CYC dose was 112±5.6 g and duration of CYC treatment was 87±21.2 months in patients with bladder cancer. The mean CYC dose was significantly higher for (ever-oral po or IV+po) versus IV only routes (10.3±5.6 vs. 32.8±28.5 gram respectively, p&lt;0.001). In addition hemorrhagic cystitis incidence was found higher in ever-oral than IV only routes groups [4/80 (5%) vs. 4/576 (0.7%) respectively, HR:3.9, CI:0.9-15.9, p=0.056]. <h3>Conclusions</h3> Bladder toxicity is associated with cumulative CYC dose and its oral administration and could be higher in patients with SSc. However, no preventive effect of mesna on hemorrhagic cystitis was shown. <h3>Disclosure of Interest</h3> None Declared
Lymph Node Uptake of Tc-99m MDP in Hodgkin's Disease
Authors: HARENDA H. MEHTA, CHRISTOPHER J. PALESTRO
Journal: Clinical Nuclear Medicine (1997)

Extraosseous accumulation of bone agents occurs in a variety of conditions including tumor, trauma, infarct, surgical scar, and occasionally, infection. Lymph node uptake has been described, and is typically related to subcutaneous infiltration of tracer at the time of injection. The authors have recently observed lymph node uptake of Tc-99m MDP, remote from any injection site, in a patient with Hodgkin's disease.
Mid Staffordshire hospital trust's services will be divided between two neighbouring hospitals
Authors: C. Dyer
Journal: BMJ (2014)

Mid Staffordshire NHS Foundation Trust, which was hit by one of the worst scandals over poor quality care in NHS history, is to be dissolved.

The health secretary for England, Jeremy Hunt, confirmed that management of the trust’s two hospitals, Stafford and Cannock Chase, would be transferred to neighbouring NHS trusts and that services at Stafford Hospital would be downgraded.

Hunt, who had the final say, accepted the recommendations of three trust special administrators appointed to tackle Mid Staffordshire’s burgeoning deficit and to draw up a plan to ensure clinical and financial stability.1

But in a departure from the administrators’ …
Activation of the AMPK regulated metabolic stress response by a small molecule HER2/EGFR tyrosine kinase inhibitor protects cardiac myocytes from apoptotic stimuli
Authors: S. S. Bacus, J. E. Hill, P. Trusk, R. Seger, N. L. Spector
Journal: Journal of Clinical Oncology (2007)

14000 Background: The HER2 receptor tyrosine kinase is a survival factor for human cardiomyocytes, providing a potential explanation for the increased incidence of cardiomyopathy associated with anti-HER2 monoclonal antibody trastuzumab. Here we show that GW2974, a HER2/EGFR TKI, but not trastuzumab activates AMP kinase (AMPK), initiating a metabolic stress response in human cardiomyocytes that protects against TNFa induced cell death. GW2974 stimulates calcium dependent fatty acid oxidation in vitro resulting in upregulation of ATP and in myocardium of GW2974 treated rodents. Methods: Western blot: p-Akt, p-Erk1/2, p-AMPKa and p- eEF2 (Cell Signaling); ERRa, ERR? (R&amp;D Systems); PGC-1 (Chemicon); MCAD (Cayman Chemicals); Heregulin, NF?B, and Actin (Sigma). ATP was performed utilizing a bioluminescence assay kit H52 (Roche). Lipid staining was done with Oil Red O (Sigma). Cells: Au565 breast cancer and primary human cardiomyocytes (HMC) were grown in RPMI supplemented with 15% BFS treatments. BAPTA/AM and Compound C (Calbiochem); GW2974 and TNFa (Sigma); trastuzumab (Genentech). Results: Our results show that treatment with GW2974 activates catabolic pathways by activation of AMPK. AMPK is a key regulator in mitochondrial energy producing pathways in human cardiac cells. Phosphorylation of AMPK resulted in phosphorylation of eEF2, upregulation of ERRa and PGC-1 and upregulation of ATP levels. AMPK activation depends on Ca ++ as the calcium chelation abolished it. Trastuzumab and Gleevec failed to activate AMPK survival pathways. In addition, GW2974 protected cardiac cells from TNFa killing, whereas treatment with TNFa and trastuzumab resulted in pervasive cellular death. Inhibition of AMPK by Compound C or siRNA resulted in cardiomyocyte killing. Conclusion: Activation of AMPK and its effects on metabolic pathways and energy production in HMC may explain the apparent reduced risk of cardiotoxicity associated with HER2 TKI compared with trastuzumab in treating patients with HER2 overexpressing breast cancers. Although activation of AMPK protected normal cardiac myocytes, this effect appears to be lethal to sensitive HER2 overexpressing breast cancer cells, which are “addicted” to glycolysis. No significant financial relationships to disclose.
Causes and Outcomes of the Acute Chest Syndrome in Sickle Cell Disease
Authors: Elliott P. Vichinsky, Lynne D. Neumayr, Ann N. Earles, Roger Williams, Evelyne T. Lennette, Deborah Dean, Bruce Nickerson, Eugene Orringer, Virgil McKie, Rita Bellevue, Charles Daeschner, Miguel Abboud, Mark Moncino, Samir Ballas, Russell Ware, Elizabeth A. Manci
Journal: New England Journal of Medicine (2000)

The acute chest syndrome is the leading cause of death among patients with sickle cell disease. Since its cause is largely unknown, therapy is supportive. Pilot studies with improved diagnostic techniques suggest that infection and fat embolism are underdiagnosed in patients with the syndrome.
AB1434-HPR Recreational and physical activities and use of free time in patients with rheumatoid and relationship with disease activity
Authors: L. Villarreal, J. Bello, L. Amador, A. Urbina, D. Zambrano, P. Santos-Moreno
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA), as known, causes inability in various performance areas mostly in the musculoskeletal. Reduced physical activity, substantial disability and poor general health perception have previously been described in people with RA. <h3>Objectives</h3> The aim of this study was to describe the socio-demographic profile, recreational and physical activity and use of free time in a cohort of patients with RA in a specialized clinic. <h3>Methods</h3> A descriptive cross-sectional study was performed in a specialized clinic dedicated to care patients with RA. 252 patients were included in the study, which were seen by the area of psychology, which information was collected through semi-structured interviews and non-probability sampling. Descriptive epidemiology was applied for continuous variables, measures of central tendency and dispersion for categorical/qualitative variables and Pearson's statistics for bi-variated analysis. <h3>Results</h3> Total sample of patients was 252, 214 (84.9%) were women and 38 (15.1%) were men. Patients had a DAS28-3.52±0.85 in average. Medium age is 56.9±9 years; 44.4% of patients were medium socio-economical level and the 40.9% were low socio-economical level; 36% was married, 19.8% is divorced, 15.5% is single and others undefined. Related with the occupation, 31% is retired because age and the 17.9% have handicap retirement pay; 19.4% is dedicated to the housekeeping and 31.7% were working. Related to education 19.4% no education, 25% had elementary school, 29% didn't finish high school, 18.2 were technical and only 8.4% finish high school. Finally, 54% of patients had mixed activities (recreational, housekeeping, intellectual and sports), 12.7% only housekeeping, 12.3% sports, 17.7% others and 3.3% didn't have any activities because great disability. Women show interest in mixed activities (46.3%), housekeeping (23.4%), sports (11.2%) and others (19.1%). On the other hand, in men were mixed activities (63.2%), sports (18.4%) and others (18.4%). It was established a correlation between a low level of activities and higher disease activity using DAS28 (p&lt;0.008). <h3>Conclusions</h3> Men and women using free time had predominantly mixed activities, but men like more make sports and women like more housekeeping; higher DAS28 is correlated with fewer level of recreational activity. According to these findings there is a prevalence of patients with low-medium socio-economical levels in RA which shows a possible correlation of a socio-demographic unfavorable situation with disease. <h3>Disclosure of Interest</h3> None Declared
OP0059 The Coexistance of Osteoarthritis and Neuropathic Pain
Authors: D. Evcik, S. Kibar, S. Ay, E. Yıldız
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The discordance between the structural damage and the severity of the pain in knee osteoarthritis (OA) suggests the effect of central and peripheral sensitization mechanisms on pain perception. This comes into the question of whether the characteristics of neuropathic pain (NP) exist in OA. <h3>Objectives</h3> To investigate the existency of NP features in osteoarthritis patients. <h3>Methods</h3> A total of 103 patients with knee pain lasting at least 3 months and diagnosed as knee OA based on the criteria of American College of Rheumatology were included in this study. The patients having any disease that may cause NP and having NP medication were excluded. The patients9 knee radiographies were graded according to Kellgren Lawrence criteria. The patients were allocated in two groups; as grade I-II (Group 1) and grade III-IV (Group2). The frequency of NP were evaluated by The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale and Neuropathic Pain Diagnostic Questionnaire (DN4). Additionally the pain at rest and the activity were measured by Visual Analogue Scale (VAS), functional level was assessed by by Knee Outcome Survey-Activities for Daily Living Scale (KOS-ADSL) and quality of life was evaluated by Nottingham Health Profile (NHP). <h3>Results</h3> The mean ages of group 1 and group two were 59.74 and 67.30 respectively. The ratio of the results of LANNS and DN4 in group 1 was 10% and 79.2% in goup 2. There were statistically significant differences in group 2 in LANNS, DN-4, VAS, KOS-ADSL, NHP scores (p&lt;0.001). A positive correlation between NP scores (LANNS, DN-4) and the grades of disease was determined (p&lt;0.0001, r=0,80 ve 0,81 respectively). Also there was a positive correlation between NP (LANNS and DN-4) scores and KOS-ADSL (p&lt;0.001, r=0,84 and 0.83). However LANNS and DN-4 were negatively correlated with NHP (p&lt;0.001, r=-0.88 ve -0.87). <h3>Conclusions</h3> The coexistence of NP increases with the progression of osteoarthritis. NP seems to have negative effects on functional level and quality of life. While planning a treatment program for progressive OA, NP should be kept in mind program of. <h3>References</h3> Finan PH, Buenaver LF, Bounds SC, et al. Discordance between pain and radiographic severity in knee osteoarthritis: findings from quantitative sensory testing of central sensitization. Arthritis Rheum. 2013;65(2):363-72. doi: 10.1002/art.34646. Allen K. Central pain contributions in osteoarthritis: next steps for improving recognition and treatment? Arthritis Res Ther. 2011;13(6):133. doi: 10.1186/ar3499. Ohtori S, Orita S, Yamashita M, et al. Existence of a neuropathic pain component in patients with osteoarthritis of the knee. Yonsei Med J. 2012 Jul 1;53(4):801-5. doi: 10.3349/ymj.2012.53.4.801. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4929