tbuckley/cabot-search huggingface dataset:
Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice
Authors: Vivian P Bykerk, Andrew J K Östör, José Alvaro-Gracia, Karel Pavelka, José Andrés Román Ivorra, Winfried Graninger, William Bensen, Michael T Nurmohamed, Andreas Krause, Corrado Bernasconi, Andrea Stancati, Jean Sibilia
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To evaluate the safety and efficacy of tocilizumab in clinical practice in patients with rheumatoid arthritis (RA) with inadequate responses (IR) to disease-modifying antirheumatic drugs (DMARDs) or both DMARDs and tumour necrosis factor α inhibitors (TNFis). <h3>Methods</h3> Patients—categorised as TNFi-naive, TNFi-previous (washout) or TNFi-recent (no washout) —received open-label tocilizumab (8 mg/kg) every 4 weeks ± DMARDs for 24 weeks. Adverse events (AEs) and treatment discontinuations were monitored. Efficacy end points included American College of Rheumatology (ACR) responses, 28-joint disease activity score (DAS28) and European League Against Rheumatism responses. <h3>Results</h3> Overall, 1681 (976 TNF-naive, 298 TNFi-previous and 407 TNFi-recent) patients were treated; 5.1% discontinued treatment because of AEs. The AE rate was numerically higher in TNFi-recent (652.6/100 patient-years (PY)) and TNFi-previous (653.6/100PY) than in TNFi-naive (551.1/100PY) patients. Serious AE rates were 18.0/100PY, 28.0/100PY and 18.6/100PY; serious infection rates were 6.0/100PY, 6.8/100PY and 4.2/100PY, respectively. At week 4, 36.5% of patients achieved ACR20 response and 14.9% DAS28 remission (&lt;2.6); at week 24, 66.9%, 46.6%, 26.4% and 56.8% achieved ACR20/ACR50/ACR70 responses and DAS28 remission, respectively. Overall, 61.6% (TNFi-naive), 48.5% (TNFi-previous) and 50.4% (TNFi-recent) patients achieved DAS28 remission. <h3>Conclusions</h3> In patients with RA who were DMARD-IR/TNFi-IR, tocilizumab ± DMARDs provided rapid and sustained efficacy without unexpected safety concerns.
Combined measurements of neuron specific enolase and bombesin/gastrin releasing peptide in lung cancer
Authors: GV Scagliotti, M Piani, E Gatti, F Gozzelino, C Albera, E Pozzi
Journal: European Respiratory Journal (1989)

Pretreatment serum neuron specific enolase (NSE) and plasma bombesin/gastrin releasing peptide (BN/GRP) were measured in 92 lung cancer patients and 17 controls. The mean level of NSE (p less than 0.001) and BN/GRP (p less than 0.05) was significantly raised in patients with small cell lung cancer (SCLC, n = 62) compared to non-SCLC (n = 30) and controls. The mean concentration of NSE in extensive SCLC was significantly greater (p less than 0.005) than in limited stage but with a substantial overlap of values. Forty-seven out of 62 SCLC patients had at least one of the two markers raised (sensitivity 76%, specificity 83%), 44 had raised NSE (sensitivity 71%, specificity 89%) but only 24 had BN/GRP raised (sensitivity 42%, specificity 91%). At restaging, 16 of 19 patients with SCLC responsive to chemotherapy showed a significant fall of NSE; on the other hand, BN/GRP fell significantly in only 3 patients, remaining unchanged in the majority of responding patients. In conclusion, the combined determination of NSE and BN/GRP in SCLC, at diagnosis and during the follow-up, was not found to be superior to NSE determination alone.
Human lung mast cells modulate the functions of airway smooth muscle cells in asthma
Authors: H. Alkhouri, F. Hollins, L. M. Moir, C. E. Brightling, C. L. Armour, J.M. Hughes
Journal: Allergy (2011)

Activated mast cell densities are increased on the airway smooth muscle in asthma where they may modulate muscle functions and thus contribute to airway inflammation, remodelling and airflow obstruction.To determine the effects of human lung mast cells on the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma.Freshly isolated human lung mast cells were stimulated with IgE/anti-IgE. Culture supernatants were collected after 2 and 24 h and the mast cells lysed. The supernatants/lysates were added to serum-deprived, subconfluent airway smooth muscle cells for up to 48 h. Released chemokines and extracellular matrix were measured by ELISA, proliferation was quantified by [(3) H]-thymidine incorporation and cell counting, and intracellular signalling by phospho-arrays.Mast cell 2-h supernatants reduced CCL11 and increased CXCL8 and fibronectin production from both asthmatic and nonasthmatic muscle cells. Leupeptin reversed these effects. Mast cell 24-h supernatants and lysates reduced CCL11 release from both muscle cell types but increased CXCL8 release by nonasthmatic cells. The 24-h supernatants also reduced asthmatic, but not nonasthmatic, muscle cell DNA synthesis and asthmatic cell numbers over 5 days through inhibiting extracellular signal-regulated kinase (ERK) and phosphatidylinositol (PI3)-kinase pathways. However, prostaglandins, thromboxanes, IL-4 and IL-13 were not involved in reducing the proliferation.Mast cell proteases and newly synthesized products differentially modulated the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Thus, mast cells may modulate their own recruitment and airway smooth muscle functions locally in asthma.
Localized Fibrous Tumor of the Liver: Imaging Features
Authors: Thomas Moser, Tereza S. Nogueira
Journal: Liver Cancer (2009)

Also known as solitary fibrous tumors, or localized fibrous mesothelioma, localized fibrous tumors (LFTs) can occur in numerous different locations including most organs and soft tissues. The archetype of this entity has been described in the pleura, where it accounts for 5% of tumors. On the other hand, LFT of the liver is a very infrequent tumor with no more than 30 cases reported in the English language literature. Hepatic LFT usually manifests with vague abdominal complaints or even mildly abnormal liver blood tests. However, some patients remain asymptomatic and the tumor represents an incidental finding. It generally attains large size before discovery. Patients may also present with hypoglycemia as a paraneoplastic manifestation. Definitive diagnosis of LFT reposes on histology coupled with the characteristic immunological labeling for CD34.Imaging studies may sometimes suggest the diagnosis. As for any hepatic tumor, multiphasic acquisition, either at computed tomography (CT) scan or magnetic resonance imaging (MRI), is required. It means that after intravenous injection of contrast media, images are obtained during maximal hepatic artery and portal and hepatic veins opacification (~30 and 70 s following the beginning of injection, respectively). Occasionally, delayed images are also obtained (at 5 min or more). Contrast uptake within hepatic lesions is analyzed with respect to these different phases, enabling tumor characterization. For example, hypervascular tumors enhance simultaneously to the hepatic artery. Hypovascular tumors disclose only mild or absent enhancement during the portal phase. Lesions containing a fibrous contingent may enhance only during the delayed phase. Such delayed enhancement is believed to correspond to interstitial contrast diffusion through collagen fibers.
Association between a polymorphism in the G protein β3 subunit gene (GNB3) with arterial hypertension but not with myocardial infarction
Authors: C Hengstenberg
Journal: Cardiovascular Research (2001)

Objective: A polymorphism at position 825(C→T) of the G protein β3 (GNB3) gene was found to be associated with enhanced transmembrane signalling as well as with an increased prevalence of arterial hypertension. The aim of the present study was to further investigate the association of the GNB3 C825T allele status with arterial hypertension in a large population-based sample and its association with specific end organ damage, i.e. myocardial infarction (MI). Methods: Individuals from a population-based sample (n = 2052) and patients suffering from premature MI (age at first MI ≤60 years, n = 606) were studied by questionnaire as well as by physical examination and biochemical analyses. Results: In the population-based sample, the prevalence of arterial hypertension (blood pressure ≥160/95 mmHg and/or antihypertensive medication) was higher in individuals with the TT genotype (41.8%) as compared to heterozygote individuals (36.6%) or those with the CC genotype (32.75%) (P = 0.02). This association was predominantly found in men. Moreover, men without antihypertensive medication carrying the TT genotype showed higher diastolic blood pressure than those carrying the CC genotype (86.5 vs. 83.7 mmHg, P = 0.04). However, the genotype distribution and the allele frequencies were similar in both, the population-based and the MI patient sample. Furthermore, neither the age at the time of MI nor the location of the MI were related to the genotype distribution. Similarly, gender and age stratified analyses did not show any association of the GNB3 genotype and MI. Conclusions: In male individuals from a large population-based sample, the T allele of the GNB3 polymorphism was associated with arterial hypertension. However, the effects of the GNB3 825T allele on blood pressure were small and did not translate to a clinically relevant increase of risk for MI.
Statistical Investigation of Correlations Between Serum Potassium Levels and Electrocardiographic Findings in Patients on Intermittent Hemodialysis Therapy
Authors: PETER P. FROHNERT, EMILIO R. GLULIANI, MORDECAI FRIEDBERG, WILLIAM J. JOHNSON, W. NEWLON TAUXE
Journal: Circulation (1970)

Simultaneous determinations of serum potassium and sodium, blood pH, blood pressure, and 12-lead electrocardiograms were obtained in hyperkalemic patients with chronic renal failure. Statistical investigation of the data showed a high correlation between serum potassium levels and ventricular repolarization abnormalities. "Mean intracellular potassium concentration" derived from total body potassium and total body water values was not accurate enough to show significant correlations to ECG changes and did not improve on the already significant correlations with serum potassium levels. Equations are presented which would permit the estimation of serum potassium levels (in a narrow range) from electrocardiographic findings in patients with chronic renal failure and suspected hyperkalemia.
Paraneoplastic Acanthosis Nigricans With Cutaneous and Mucosal Papillomatosis Preceding Recurrence of a Gastric Adenocarcinoma
Authors: Karsten Schulmann, Katharina Strate, Christian P. Pox, Ulrike Wieland, Alexander Kreuter
Journal: Journal of Clinical Oncology (2012)

Recurrence of a Gastric Adenocarcinoma Case ReportA 52-year old man was diagnosed with a human epidermal growth factor receptor 2-negative signet cell carcinoma of the stomach in February 2011.Staging examinations showed an uT3uN2cM1 stage with limited distant metastasis consisting of an isolated aortointercaval lymph node metastasis.The patient was treated with four cycles of fluorouracil, leukovorin, and docetaxel in a neoadjuvant intention.R0 gastrectomy with D2 lymphadenectomy and resection of the aortointercaval lymph node metastasis was performed in May 2011.The gastric cancer showed marked tumor regression, whereas the lymph node metastasis did not.Postoperative tumor stage was ypT2, ypN3 with 23 of 39 positive lymph nodes, and pM1 status as a result of the aortointercaval metastasis.The patient received four adjuvant cycles of fluorouracil, leukovorin, and docetaxel until July 2011.Computed tomography (CT) scans in September 2011 were without evidence of recurrence or residual disease.In October 2011, the patient presented with extensive generalized pruritus.To rule out a paraneoplastic cause, repeated CT scans were performed and did not show any evidence of recurrent disease.CA72-4 was slightly increased (23 U/mL), and carcinoembryonic antigen was normal.The patient was
A novel flow cytometric approach reveals abundant CD8+ T cell derived microvesicles in rheumatoid arthritis synovial fluid samples
Authors: Bence Gyorgy, Matthew Wright, Gyorgy Nagy, Kalman Toth, Anna Polgar, Gergo Zelenak, Istvan Borocz, Lilla Turiak, Petra Herczeg, Zsigmond Ledeczi, Beata Derfalvi, Karoly Vekey, Agnes Kittel, Steffen Gay, Andras Falus, Edit I Buzas
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> Microvesicle (MV) secretion represents an evolutionally conserved feature of all living cells. The assessment of MVs may give insight into the pathomechanism of various disorders. Furthermore, it may serve as potential novel biomarker of disease. However, the characterisation of MVs in body fluids has not been fully standardised yet, and there are numerous pitfalls that hinder the correct assessment of MVs. Previously, the authors developed a 'differential detergent lysis' method to exclude MV-mimicking protein aggregates and immune complexes during flow cytometry. Using our novel method here the authors analysed synovial fluid (SF) derived MVs. <h3>Materials and methods</h3> The authors tested plasma and SF samples of patients with osteoarthritis (OA), rheumatoid arthritis (RA) and juvenile idiopathic arthritis. The authors used electron microscopy and nanoparticle tracking analysis (NTA) to determine the particle size distributions in SF samples. The authors also applied mass spectrometry to determine the MV protein composition in SFs. To immune phenotype SF MVs, the authors applied flow cytometry using 'differential detergent lysis' method. <h3>Results</h3> The different techniques gave concordant results regarding the size distribution of MVs in SF samples (80–400 nm). However, NTA analysis and MS revealed that most of the events were related to protein aggregates rather than cell-derived vesicles. Using our novel flow cytometric approach, the authors demonstrate for the first time that CD3+ and CD8+ T cell derived SF MVs are highly elevated in SFs of patients with RA compared to OA patients (p=0.027 and p=0.009, respectively after Bonferroni corrections). In contrast, T cell derived MVs were undetectable in the blood plasma of patients with OA or RA. B cell and T cell derived MV counts strongly correlated with rheumatoid factor positivity in RA (r=0.912, p=0.002 and r=0.956, p=0.001, respectively). <h3>Conclusions</h3> The correct assessment of MVs in RA suggests local CD8+ T cell activation in the joints and may shed light on hidden immunpathological processes of this disease.
849 ALISPORIVIR INTERFERON-FREE TREATMENT ACHIEVED COMPARABLE EARLY HCV CLEARANCE RATES IN BOTH IL28CC AND IL28 CT/TT PATIENTS INFECTED WITH GENOTYPE 2/3 HCV
Authors: Y. Li, J. Yu, M. Levi, G. Nabel, C. Hurwitz, M. Healey, W. Bao, L. Li, K.J. Johnson, C. Avila, N.V. Naoumov, B. Li
Journal: Journal of Hepatology (2013)
TNF-alpha dependent production of inducible nitric oxide is involved in PGE1 protection against acute liver injury
Authors: J Muntane
Journal: Gut (2000)

Tumour necrosis factor alpha (TNF-alpha) and nitric oxide modulate damage in several experimental models of liver injury. We have previously shown that protection against D-galactosamine (D-GalN) induced liver injury by prostaglandin E(1) (PGE(1)) was accompanied by an increase in TNF-alpha and nitrite/nitrate in serum.The aim of the present study was to evaluate the role of TNF-alpha and nitric oxide during protection by PGE(1) of liver damage induced by D-GalN.Liver injury was induced in male Wistar rats by intraperitoneal injection of 1 g/kg of D-GalN. PGE(1) was administered 30 minutes before D-GalN. Inducible nitric oxide synthase (iNOS) was inhibited by methylisothiourea (MT), and TNF-alpha concentration in serum was lowered by administration of anti-TNF-alpha antibodies. Liver injury was evaluated by alanine aminotransferase activity in serum, and histological examination and DNA fragmentation in liver. TNF-alpha and nitrite/nitrate concentrations were determined in serum. Expression of TNF-alpha and iNOS was also assessed in liver sections.PGE(1) decreased liver injury and increased TNF-alpha and nitrite/nitrate concentrations in serum of rats treated with D-GalN. PGE(1) protection was related to enhanced expression of TNF-alpha and iNOS in hepatocytes. Administration of anti-TNF-alpha antibodies or MT blocked the protection by PGE(1) of liver injury induced by D-GalN.This study suggests that prior administration of PGE(1) to D-GalN treated animals enhanced expression of TNF-alpha and iNOS in hepatocytes, and that this was causally related to protection by PGE(1) against D-GalN induced liver injury.
Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: an open-label randomised trial
Authors: Benjamin H Chi, Moses Sinkala, Felistas Mbewe, Ronald A Cantrell, Gina Kruse, Namwinga Chintu, Grace M Aldrovandi, Elizabeth M Stringer, Chipepo Kankasa, Jeffrey T Safrit, Jeffrey SA Stringer
Journal: The Lancet (2007)
Is risk of fast bowling injury in cricketers greatest in those who bowl most? A cohort of young English fast bowlers
Authors: P L Gregory, M E Batt, W A Wallace
Journal: British Journal of Sports Medicine (2004)

To determine whether young fast bowlers are exceeding directives limiting bowling and how incidence of fast bowling injury varies with amount of bowling.A prospective cohort study of injuries sustained by 70 fast bowlers (mean (SD) age 15.3 (2.4) years) was undertaken. Bowlers were recruited from the Centres of Excellence of three "First Class" counties in England in January 1998. Details of injuries were collected by telephone questionnaire every six weeks for six months from each bowler. The number of balls bowled in matches and practices by each bowler was recorded. The cohort was divided into groups according to the number of balls bowled in the study period, and bowling injury incidences were calculated for each group.All injuries caused by bowling and interfering with bowling.Telephone follow up was achieved when planned on 97.9% of occasions. There were 23 bowling injuries reported in the study period that met the inclusion criteria. The overall incidence of bowling injury in the study period was 32.8 per 100 fast bowlers. The incidence of bowling injury for the 15 bowlers who bowled less than 1000 balls in the study period was 20.0 per 100 fast bowlers. The incidence for the 32 who bowled 1000-2000 balls was 37.5 per 100 fast bowlers. The incidence for the 14 who bowled 2000-3000 balls was 35.7 per 100. The incidence for the nine who bowled more than 3000 balls was 33.3 per 100.The expected increased incidence of bowling injury in young fast bowlers who bowl most was not observed, although more than 12% exceeded the recommended limit.
Remodeling of Early-Phase Repolarization
Authors: Yanggan Wang, Jun Cheng, Ronald W. Joyner, Mary B. Wagner, Joseph A. Hill
Journal: Circulation (2006)

The early phase of action potential (AP) repolarization is critical to impulse conduction in the heart because it provides current for charging electrically coupled cells. In the present study we tested the impact of heart failure-associated electrical remodeling on AP propagation.Subepicardial, midmyocardial, and subendocardial myocytes were enzymatically dissociated from control and pressure-overload failing left ventricle (LV), and APs were recorded. A unique coupling-clamp technique was used to electrically couple 2 isolated myocytes with a controlled value of coupling conductance (Gc). In sham-operated mice, AP duration manifested a clear transmural gradient, with faster repolarization in subepicardial myocytes than in subendocardial myocytes. AP propagation from subendocardial to subepicardial myocytes required less Gc compared with conduction in the opposite direction. In failing heart, AP morphology was dramatically altered, with a significantly elevated plateau potential and prolonged AP duration. Spatially nonuniform alteration of AP duration in failing heart blunted the transmural gradient of repolarization. Furthermore, increased pacing rate prolonged AP duration exclusively in myocytes from failing heart, and the critical conductance required for successful AP propagation decreased significantly at high frequencies. Finally, in failing heart, asymmetry of transmural electrical propagation was abolished.In failing heart, preferential conduction from subendocardial to subepicardial myocytes is lost, and failing myocytes manifest facilitated AP propagation at fast rates. Together, these electrical remodeling responses may promote conduction of premature impulses and heighten the risk of malignant arrhythmia, a prominent feature of heart failure.
Cancer Inhibition through Circadian Reprogramming of Tumor Transcriptome with Meal Timing
Authors: Xiao-Mei Li, Franck Delaunay, Sandrine Dulong, Bruno Claustrat, Sinisa Zampera, Yoshiro Fujii, Michèle Teboul, Jacques Beau, Francis Lévi
Journal: Cancer Research (2010)

Abstract Circadian disruption accelerates cancer progression, whereas circadian reinforcement could halt it. Mice with P03 pancreatic adenocarcinoma (n = 77) were synchronized and fed ad libitum (AL) or with meal timing (MT) from Zeitgeber time (ZT) 2 to ZT6 with normal or fat diet. Tumor gene expression profiling was determined with DNA microarrays at endogenous circadian time (CT) 4 and CT16. Circadian mRNA expression patterns were determined for clock genes Rev-erbα, Per2, and Bmal1, cellular stress genes Hspa8 and Cirbp, and cyclin A2 gene Ccna2 in liver and tumor. The 24-hour patterns in telemetered rest-activity and body temperature and plasma corticosterone and insulin-like growth factor-I (IGF-I) were assessed. We showed that MT inhibited cancer growth by ∼40% as compared with AL (P = 0.011) irrespective of calorie intake. Clock gene transcription remained arrhythmic in tumors irrespective of feeding schedule or diet. Yet, MT upregulated or downregulated the expression of 423 tumor genes, according to CT. Moreover, 36 genes involved in cellular stress, cell cycle, and metabolism were upregulated at one CT and downregulated 12 h apart. MT induced &amp;gt;10-fold circadian expression of Hspa8, Cirbp, and Ccna2 in tumors. Corticosterone or IGF-I patterns played no role in tumor growth inhibition. In contrast, MT consistently doubled the circadian amplitude of body temperature. Peak and trough respectively corresponded to peak expressions of Hspa8 and Cirbp in tumors. The reinforcement of the host circadian timing system with MT induced 24-hour rhythmic expression of critical genes in clock-deficient tumors, which translated into cancer growth inhibition. Targeting circadian clocks represents a novel potential challenge for cancer therapeutics. Cancer Res; 70(8); 3351–60. ©2010 AACR.