tbuckley/cabot-search huggingface dataset:
CLinical experience acquired with the efalizumab (Raptiva<sup>®</sup>) (CLEAR) trial in patients with moderate-to-severe plaque psoriasis: results from a phase III international randomized, placebo-controlled trial
Authors: L. Dubertret, W. Sterry, J.D. Bos, S. Chimenti, S. Shumack, C.G. Larsen, N.H. Shear, K.A. Papp
Journal: British Journal of Dermatology (2006)

Background Efalizumab (anti‐CD11a), a humanized monoclonal antibody, blocks multiple T‐cell‐dependent functions implicated in the pathogenesis of psoriasis, including T‐cell activation, migration to the skin, reactivation in psoriatic skin and interactions with keratinocytes. Objectives This multinational, randomized, double‐blind, placebo‐controlled, parallel‐group trial was designed to evaluate the safety and efficacy of subcutaneous efalizumab 1·0 mg kg−1 once weekly for 12 weeks compared with placebo in a population that included high‐need patients, defined as those for whom at least two systemic therapies were unsuitable because of lack of efficacy, intolerance or contraindication. Patients/methods Patients with moderate‐to‐severe plaque psoriasis [involvement of ≥ 10% of total body surface area and Psoriasis Area and Severity Index (PASI) ≥ 12·0 at screening] were randomized in a 2 : 1 ratio to receive efalizumab or placebo. The primary efficacy endpoint was the proportion of patients achieving ≥ 75% PASI improvement (PASI‐75 response) at week 12 in the intention‐to‐treat population; secondary endpoints included changes in PASI, static Physician's Global Assessment, Physician's Global Assessment of change from baseline and percentage of body surface area affected. Results We enrolled 793 patients (529 received efalizumab and 264 placebo), including 526 high‐need patients (342 received efalizumab and 184 placebo). Week 12 PASI‐75 rates were 29·5% for efalizumab compared with 2·7% for placebo among high‐need patients (P < 0·0001) and 31·4% for efalizumab compared with 4·2% for placebo in the full study population (P < 0·0001). Results for all secondary efficacy endpoints showed superiority of efalizumab over placebo in both the high‐need and the full populations. Efalizumab demonstrated a favourable safety profile, without evidence of systemic toxicity, in both the high‐need group and the overall study population. Conclusions The efficacy and safety of efalizumab therapy were comparable between high‐need patients and the more general moderate‐to‐severe psoriasis patient population. In view of its demonstrated efficacy and safety profile, efalizumab represents a valuable option for the treatment of adult patients with moderate‐to‐severe plaque psoriasis, including high‐need patients.
Effect of endothelin and endothelin receptor blockade on capillary permeability in experimental pancreatitis
Authors: G Eibl
Journal: Gut (2000)

<h3>BACKGROUND</h3> Capillary leakage with fluid loss into the third space contributes to many of the early systemic complications in severe acute pancreatitis. There has been increasing interest in endothelin as one of the factors affecting capillary permeability. <h3>AIM</h3> To elucidate further the role of endothelin in the development of capillary leakage in acute pancreatitis by investigating the effect of exogenous endothelin administration and endothelin receptor blockade in sham operated animals and two models of acute pancreatitis. <h3>METHODS</h3> Determination of capillary permeability in the pancreas and colonic mucosa by quantifying extravasation of fluorescein labelled dextran using a novel computer assisted video image analysis system. <h3>RESULTS</h3> Pancreatic and colonic capillary permeability increased stepwise from mild to severe acute pancreatitis. Endothelin increased pancreatic and colonic capillary permeability in healthy animals and animals with mild acute pancreatitis but had no additional adverse effect in severe acute pancreatitis. Endothelin receptor blockade decreased pancreatic capillary permeability in sham operated rats but had no effect on the colon. In mild and severe acute pancreatitis, endothelin receptor blockade stabilised increased capillary permeability in both the pancreas and colon. <h3>CONCLUSIONS</h3> Endothelin plays an important role in mediating capillary permeability in the pancreas. In severe pancreatitis, it increases capillary permeability even outside the pancreas, thereby contributing to capillary leakage. Endothelin receptor blockade significantly reduces capillary permeability in acute pancreatitis both in and outside the pancreas, suggesting a therapeutic approach to counteract capillary leakage in severe acute pancreatitis.
Authors’ response: Observations suggesting bioactive Fgf15 is not present in mouse blood
Authors: Matias A Avila
Journal: Gut (2013)

We have read with interest Dr Mats Rudling's letter regarding our recent article on the role of Fgf15 in liver regeneration and the liver growth-promoting effects of bile acids.1 Our work was based on the use of Fgf15 knockout mice, and in these mice we indeed found impaired liver regeneration and bile acid metabolism after partial hepatectomy and reduced liver cell proliferation upon bile acid feeding.2 The fact that FGFR4 deficient mice …
Measles Virus Induces Oncolysis of Mesothelioma Cells and Allows Dendritic Cells to Cross-Prime Tumor-Specific CD8 Response
Authors: Anne Gauvrit, Samantha Brandler, Carole Sapede-Peroz, Nicolas Boisgerault, Frédéric Tangy, Marc Gregoire
Journal: Cancer Research (2008)

Abstract Despite conventional medical and surgical treatments, malignant pleural mesothelioma (MPM) remains incurable. Oncovirotherapy (i.e., the use of replication-competent virus for cancer treatment) is currently explored in clinical trials. In this study, we investigated the antineoplastic potential of a new oncolytic viral agent, a live-attenuated measles virus (MV) strain derived from the Edmonston vaccine lineage (Schwarz strain). We evaluated both oncolytic activity and immunoadjuvant properties of the MV vaccine strain on mesothelioma tumor cells. Infectivity, syncytium formation, and cytolytic activity of MV were studied on a panel of mesothelioma cells derived from pleural effusions of MPM patients. We observed that MV infected preferentially MPM cell lines in comparison with nontransformed mesothelial cells, leading to an efficient killing of a significant fraction of tumor cells. A cytoreductive activity was also evidenced through formation of multinuclear cellular aggregates (syncytia). The susceptibility of MPM cell lines to measles infection was assessed by the analysis of cell surface expression of the MV vaccine receptor (CD46). We also evaluated whether MV infection of mesothelioma cells could elicit an autologous antitumor immune response. We showed that MV Schwarz strain induced apoptotic cell death of infected mesothelioma cells, which were efficiently phagocytosed by dendritic cells (DC). Loading of DCs with MV-infected MPM cells induced DC spontaneous maturation, as evidenced by the increased expression of MHC and costimulatory molecules along with the production of proinflammatory cytokines. Priming of autologous T cells by DCs loaded with MV-infected MPM cells led to a significant proliferation of tumor-specific CD8 T cells. Altogether, these data strongly support the potential of oncolytic MV as an efficient therapeutic agent for mesothelioma cancer. [Cancer Res 2008;68(12):4882–92]
The epidermal response to subepidermal inflammation
Authors: F. SCHELLANDER, R. MARKS
Journal: British Journal of Dermatology (2006)

A marked degree of hyperproliferation and hyperplasia of the epidermis secondary to experimentally induced inflammation in the corium was induced in the flank skin of guinea pigs. The substances used to evoke a granulomatous inflammation were beryllium oxide and carrageenan. The epidermal response to this subepidermal process was studied autoradiographically and it was found that the epidermal reaction was similar to that found after direct epidermal trauma such as stripping of the horny layer. It is assumed that dermal factors are responsible for initiating this epidermal reaction and their possible nature is briefly discussed.
Adjuvant Interferon Therapy for Melanoma
Authors: Barry Hancock, Keith Wheatley, Natalie Ives, Martin Gore
Journal: Journal of Clinical Oncology (2005)

(LDI), at a dose of 3 MU, reduces the risk of recurrence (hazard ratio [HR] 0.83; 95% CI, 0.75 to 0.93; P .001). This point estimate of a 17% reduction in the odds of recurrence is smaller than the treatment effect observed for HDI(26%oddsreduction;HR0.74;95%CI,0.63to0.86; P .00009), but it is not quantitatively different (test for heterogeneity: P .2). Thus, there is no clear evidence that HDI is more effective than LDI in reducing recurrence. We agree with Moschos et al that it is possible that the effect of LDI is more transient than that with HDI, but this hypothesis needs to be confirmed. The best way to do this is through an individual patient data meta-analysis. This would permit the inclusion of data with longer follow-up than in the original trial reports and the analysis of treatment effects over time. We support Dr Schuchter’s view that overall survival is the most important end point for an adjuvant therapy, so more importantly, an individual patient data meta-analysis would allow a more precise estimate of the long-term effects on survival, including by dose of interferon, against which to balance toxicity and cost. Thetwoeditorialsneatlyhighlightthecontinuingcontroversy surrounding the use of adjuvant interferon for melanoma. Dr Schuchter states that “adjuvant trials in patientswithhigh-riskresectedmelanomashouldcontinueto include a surgery alone control arm”; and Moschos et al
Reduction in sympathetic activity after long-term CPAP treatment in sleep apnoea: cardiovascular implications
Authors: J Hedner, B Darpo, H Ejnell, J Carlson, K Caidahl
Journal: European Respiratory Journal (1995)

Twelve patients with severe obstructive sleep apnoea were included in an open, long-term, prospective, follow-up study addressing the effects of nasal continuous positive airway pressure (CPAP) on sympathetic activity, cardiac structure and blood pressure. Plasma norepinephrine (P-NE) (daytime at rest), daytime and night-time urinary excretion of NE (U-NE), vanylmandelic acid and metanephrines, together with 24 h noninvasive blood pressure (BP) recording and Doppler-echocardiography, were assessed before and after a mean of 20.5 (range 14-26) months of CPAP. Average self-reported use of CPAP was 89% (range 65-100%) of time spent in bed. Resting daytime P-NE ranged 0.35-0.83 ng.ml-1, which is elevated compared to healthy controls. Only night-time U-NE, mean daytime BP and average 24 h BP were related to severity of OSA. Night-time metanephrine was related to daytime and night-time diastolic, as well as night-time systolic, BP. Left ventricular mass index (LVMI) at baseline was correlated to daytime systolic BP and P-NE. Long-term CPAP treatment reduced biochemical markers of sympathetic activity. P-NE decreased by approximately 50%, and daytime and night-time vanylmandelic acid and metanephrine by 32-54%. In contrast, there were no overall reductions in BP or LVMI. It is concluded that obstructive sleep apnoea is associated with high sympathetic activity both during sleep and waking periods. Urinary metanephrine excretion seemed to reflect blood pressure, but neither daytime nor night-time catecholamine excretion was directly related to disease severity in patients with severe obstructive sleep apnoea.(ABSTRACT TRUNCATED AT 250 WORDS)
Systematic Review and Meta-analysis of Studies Reporting Potency Rates After Robot-assisted Radical Prostatectomy
Authors: Vincenzo Ficarra, Giacomo Novara, Thomas E. Ahlering, Anthony Costello, James A. Eastham, Markus Graefen, Giorgio Guazzoni, Mani Menon, Alexandre Mottrie, Vipul R. Patel, Henk Van der Poel, Raymond C. Rosen, Ashutosh K. Tewari, Timothy G. Wilson, Filiberto Zattoni, Francesco Montorsi
Journal: European Urology (2012)
Radiolabeled Small-Molecule Ligands for Prostate-Specific Membrane Antigen: <i>In vivo</i> Imaging in Experimental Models of Prostate Cancer
Authors: Catherine A. Foss, Ronnie C. Mease, Hong Fan, Yuchuan Wang, Hayden T. Ravert, Robert F. Dannals, Rafal T. Olszewski, Warren D. Heston, Alan P. Kozikowski, Martin G. Pomper
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Prostate-specific membrane antigen (PSMA) is a cell surface protein that is overexpressed in prostate cancer, including hormone-refractory and metastatic disease. Our goal in this study was to develop a series of PSMA-based imaging agents for clinical use. Experimental Design: We have synthesized and evaluated the in vivo biodistribution of two radiolabeled urea derivatives that have high affinity for PSMA in severe combined immunodeficient mice harboring MCF-7 (breast, PSMA-negative), PC-3 (prostate, PSMA-negative), and LNCaP (prostate, PSMA-positive) xenografts. Radiopharmaceutical binding selectivity and tumor uptake were also evaluated in vivo using dedicated small animal positron emission tomography, single photon emission computed tomography, and gamma scintigraphic imaging devices. N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-[11C]methyl-l-cysteine ([11C]DCMC Ki, 3.1 nmol/L) and N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-3-[125I]iodo-l-tyrosine ([125C]DCIT Ki, 1.5 nmol/L) were synthesized using [11C]CH3I and with [125I]NaI/Iodogen, respectively. Results: At 30 minutes postinjection, [11C]DCMC and [125I]DCIT showed tumor/muscle ratios of 10.8 and 4.7, respectively, with clear delineation of LNCaP-derived tumors on imaging. MCF-7- and PC-3-derived tumors showed significantly less uptake of [11C]DCMC or [125I]DCIT. Conclusion: These results show the feasibility of imaging PSMA-positive prostate cancer using low molecular weight agents.
Anti-inflammatory effect associated with triglyceride reduction
Authors: F. Tomassini, C. Pristipino, E.V. Scabbia, M.N. De Luca, S. Baroni, D. Scribano, F. Ginnetti, W. van de Greef, A. Masori, T. Piliego, F. Andreatti
Journal: Journal of the American College of Cardiology (1998)
Rapid and early virological response to chronic hepatitis C treatment with IFN 2b or PEG-IFN 2b plus ribavirin in HIV/HCV co-infected patients
Authors: C. Payan, A. Pivert, P. Morand, S. Fafi-Kremer, F. Carrat, S. Pol, P. Cacoub, C. Perronne, F. Lunel
Journal: Gut (2007)

<b>Background and aims:</b> An algorithm based on a 2 log<sub>10</sub> decline in hepatitis C virus (HCV) RNA at week (W) 12 has been proposed in US and European recommendations for the management of patients with chronic hepatitis C treated with pegylated-interferon and ribavirin. <b>Methods:</b> We examined rapid virological response (RVR; at W2 and W4 after the initiation of therapy) in HIV/HCV co-infected patients. Using HCV RNA measurements (Versant HCV RNA 3.0, Cobas Amplicor HCV 2.0), RVR was studied in 323 patients from the ANRS HC02 RIBAVIC trial, comparing interferon α2b 3 MU ×3/week with pegylated interferon α2b 1.5 μg/kg/week, each combined with ribavirin 800 mg/day over 48 weeks. <b>Results:</b> The best positive and negative predictive values of sustained virological response (SVR) were obtained with an undetectable HCV RNA at W4 (97%) and with more than a 2 log<sub>10</sub> decrease at W12 (99%), respectively. Prediction of non-SVR was obtained in all patients by using HCV RNA cut-off levels above 460 000 IU/ml at W4 and above 39 000 UI/ml at W12 irrespective of the HCV genotype and arm of treatment. <b>Conclusion:</b> We propose a new algorithm based on RVR thresholds using HCV RNA that allows for excellent prediction of non-SVR as early as W4.
OP0215 Baseline ASDAS and CRP Predicts Future Cardiovascular Risk in Ankylosing Spondylitis: Results After 5-Year Follow-Up
Authors: I. J. Berg, A. G. Semb, D. van der Heijde, H. Dagfinrud, T. K. Kvien, S. A. Provan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patients with ankylosing spondylitis (AS) have increased risk of cardiovascular disease (CVD), and we have previously shown in a cross-sectional study that high ASDAS is associated with atherosclerotic CVD. <h3>Objectives</h3> To investigate whether baseline AS disease activity predicts future increased arterial stiffness. <h3>Methods</h3> A 5-year follow-up study of hospital recruited AS patients diagnosed according to the mNY criteria, with examinations in 2003 and 2008-2009. Information on demographics, co-morbidities and medication was assessed from questionnaires. Baseline AS disease activity was assessed from questionnaires, clinical examination and blood samples (ASDAS-CRP, BASDAI, ESR and CRP). Arterial stiffness, measured as Augmentation index (AIx), was recorded in 2008-2009 (Sphygmocor apparatus, At Cor). Statistical analyses were performed in SPSS 20 using bivariate test as appropriate. Associations between disease activity and AIx (dependent variable) were analyzed in separate linear regression models, adjusted for age and gender using quartiles of baseline CRP, ESR and BASDAI. ASDAS was grouped according to the generally agreed cut-offs for ASDAS: inactive disease (&lt;1.3), moderate (1.3-2.0), high (2.1-3.5) and very high (&gt;3.5) disease activity. Possible confounders recorded in 2003 (smoking, BMI, level of education, use of NSAID, DMARD and TNF-inhibitors) and variables from the follow-up examination known to have a possible effect on AIx (smoking, BMI, central mean arterial pressure) were added to the model consecutively. <h3>Results</h3> 103 AS patients participated. Baseline mean (SD) age was 48.4 (12.6) years. 56 % were male, 25% smokers, 83% used NSAIDS, 17% used DMARDs, 2% used TNF-inhibitors. Mean (SD) ASDAS was 2.5 (1.2); BASDAI 4.1 (2.3). Median (IQR) ESR was (mm/h) 13 (6-24); CRP (mg/l) 4 (2-14). In linear regression models, adjusted for age and gender, higher CRP and ASDAS were significantly associated with higher AIx while ESR was borderline significant (figure). There were no associations between BASDAI and AIx. Adjustments for confounders did not alter results. <h3>Image/graph</h3> <h3>Conclusions</h3> Elevated disease activity measured by CRP and ASDAS, but not BASDAI, predicted higher future AIx, indicating that inflammation and disease activity are risk factors of CVD in AS. Reducing disease activity may be a viable way of reducing excess CVD in AS. <h3>Disclosure of Interest</h3> None Declared
Protection against a Malaria Challenge by Sporozoite Inoculation
Authors: Meta Roestenberg, Matthew McCall, Joost Hopman, Jorien Wiersma, Adrian J.F. Luty, Geert Jan van Gemert, Marga van de Vegte-Bolmer, Ben van Schaijk, Karina Teelen, Theo Arens, Lopke Spaarman, Quirijn de Mast, Will Roeffen, Georges Snounou, Laurent Rénia, Andre van der Ven, Cornelus C. Hermsen, Robert Sauerwein
Journal: New England Journal of Medicine (2009)

An effective vaccine for malaria is urgently needed. Naturally acquired immunity to malaria develops slowly, and induction of protection in humans can be achieved artificially by the inoculation of radiation-attenuated sporozoites by means of more than 1000 infective mosquito bites.
Influence of pre-analytic conditions on the rate of indeterminate T-SPOT(R).TB tests
Authors: A. Zellweger, J-P. Zellweger
Journal: European Respiratory Journal (2011)

Influence of pre-analytic conditions on the rate of indeterminate T-SPOT1.TB testsTo the Editors: A prior study has demonstrated that the rate of indeterminate T-SPOT1.TB (Oxford Immunotec, Abingdon, UK) test results performed under routine field conditions was low (3.4%) [1].Indeterminate test results were more common in individuals aged .75yrs and may be influenced by the transport conditions (cold weather in winter).Since this study was published, two technical improvements in the pre-analytic conditions were introduced.The first is the use of lithium heparinate blood sample collection tubes instead of the CPT TM Cell Preparation Tubes with sodium citrate (Vacutainer1; BD, Franklin Lakes, NJ, USA), as used in the prior study; the other is the use of the T-Cell Xtend TM reagent (Oxford Immunotec) in samples .8h old [2].
Anti-Ia Reactivity in Sera from Patients with Systemic Lupus Erythematosus
Authors: Kunio Okudaira, Robert P. Searles, Jan L. Ceuppens, James S. Goodwin, Ralph C. Williams
Journal: Journal of Clinical Investigation (1982)

Antileukocyte antibodies in sera from patients with systemic lupus erythematosus (SLE) were characterized by determining cross-reacting specificies with the antigens defined by OKT3, OKT4, OKT8, OKM1 and anti-Ia hybridoma antibodies (Abs). T cells were prepared by sheep erythrocyte (E) rosetting after removal of adherent cells. T cells, or non-T cells, were preincubated with SLE sera at 4°C and then with monoclonal Abs. Binding by specific monoclonal Abs was assessed by two methods: rosetting with ox erythrocytes conjugated with goat anti-mouse IgG and also in the fluorescence-activated cell sorter using fluorescein isothiocyanate-conjugated goat anti-mouse IgG. Using the rosetting method, we found that sera from SLE can block the binding of monoclonal mouse hybridoma anti-Ia Abs to T cells; the blocking of other monoclonal Abs was not consistent. Using fluorescence-activated cell sorter analysis, preincubation with SLE sera lowered the intensity of staining and total percentage of either T or non-T cells stained by monoclonal anti-Ia Abs. Blocking of anti-Ia Abs binding by SLE sera was not histocompatibility leukocyte antigen (HLA)-DR restricted and was not due to Fc receptor binding. These results indicated that antibodies in SLE sera react with structures contiguous to or identical with Ia determinants. Anti-Ia activities in SLE sera correlate with SLE disease activity. In addition, there was a significant negative correlation between anti-Ia blocking activity in the sera and the percentage of Ia-positive T cells in the blood of SLE patients. Antibodies in SLE sera with anti-Ia blocking activity may play an important role in immune dysregulation in SLE patients.
Trends in Hyperinsulinemia Among Nondiabetic Adults in the U.S.
Authors: Chaoyang Li, Earl S. Ford, Lisa C. McGuire, Ali H. Mokdad, Randie R. Little, Gerald M. Reaven
Journal: Diabetes Care (2006)

Insulin resistance and compensatory hyperinsulinemia have been proposed as increasing risk for a variety of abnormalities and clinical syndromes, including type 2 diabetes and cardiovascular disease. Our aim was to assess the trends in the mean concentrations of fasting serum insulin and the prevalence of hyperinsulinemia among nondiabetic adults during the periods of 1988-1994 and 1999-2002 in the U.S.