tbuckley/cabot-search huggingface dataset:
Bevacizumab salvage therapy following progression in high-grade glioma patients treated with VEGF receptor tyrosine kinase inhibitors
Authors: B. J. Scott, E. C. Quant, M. B. McNamara, P. A. Ryg, T. T. Batchelor, P. Y. Wen
Journal: Neuro-Oncology (2010)

Agents targeting the vascular endothelial growth factor (VEGF) pathway are being used with increasing frequency in patients with recurrent high-grade glioma. The effect of more than one antiangiogenic therapy given in succession has not been established. We reviewed the efficacy of bevacizumab, a VEGF-A monoclonal antibody, in patients who progressed following prior therapy with VEGF receptor tyrosine kinase inhibitors (R-TKi). Seventy-three patients with recurrent high-grade gliomas received VEGF R-TKi (cediranib, sorafenib, pazopanib, or sunitinib) as part of phase I or II clinical trials. Twenty-four of these patients with glioblastoma progressed and received bevacizumab-containing regimens immediately after R-TKi. Those who stopped R-TKi therapy for reasons other than disease progression, or received a treatment that did not include bevacizumab, were excluded from the analysis. The efficacy of bevacizumab-containing regimens in these 24 patients was evaluated. During R-TKi therapy, 6 of 24 patients (25%) had a partial response (PR) to treatment. The 6-month progression-free survival (APF6) was 16.7% and median time-to-progression (TTP) was 14.3 weeks. Grade III/IV toxicities were seen in 13 of 24 patients (54%). Subsequently with bevacizumab salvage therapy, 5 of 24 patients (21%) had a PR, the APF6 was 12.5%, and the median TTP was 8 weeks. Five of 24 patients had grade III/IV toxicities (21%). The median overall survival (OS) from the start of R-TKi therapy was 9.2 months (range: 2.8-34.1+), whereas the median OS after bevacizumab was 5.2 months (range: 1.3-28.9+). Bevacizumab retains modest activity in high-grade glioma patients who progress on R-TKi. However, the APF6 of 12.5% in this cohort of patients indicates that durable tumor control is not achieved for most patients.
Complementary Dendritic Cell–activating Function of CD8+ and CD4+ T Cells
Authors: Robbie B. Mailliard, Shinichi Egawa, Quan Cai, Anna Kalinska, Svetlana N. Bykovskaya, Michael T. Lotze, Martien L. Kapsenberg, Walter J. Storkus, Pawel Kalinski
Journal: The Journal of Experimental Medicine (2002)

Dendritic cells (DCs) activated by CD40L-expressing CD4+ T cells act as mediators of "T helper (Th)" signals for CD8+ T lymphocytes, inducing their cytotoxic function and supporting their long-term activity. Here, we show that the optimal activation of DCs, their ability to produce high levels of bioactive interleukin (IL)-12p70 and to induce Th1-type CD4+ T cells, is supported by the complementary DC-activating signals from both CD4+ and CD8+ T cells. Cord blood- or peripheral blood-isolated naive CD8+ T cells do not express CD40L, but, in contrast to naive CD4+ T cells, they are efficient producers of IFN-gamma at the earliest stages of the interaction with DCs. Naive CD8+ T cells cooperate with CD40L-expressing naive CD4+ T cells in the induction of IL-12p70 in DCs, promoting the development of primary Th1-type CD4+ T cell responses. Moreover, the recognition of major histocompatibility complex class I-presented epitopes by antigen-specific CD8+ T cells results in the TNF-alpha- and IFN-gamma-dependent increase in the activation level of DCs and in the induction of type-1 polarized mature DCs capable of producing high levels of IL-12p70 upon a subsequent CD40 ligation. The ability of class I-restricted CD8+ T cells to coactivate and polarize DCs may support the induction of Th1-type responses against class I-presented epitopes of intracellular pathogens and contact allergens, and may have therapeutical implications in cancer and chronic infections.
P126 Does a personalised and non-clinical explanation of lung health trigger the impulse in smokers to make a quit attempt?
Authors: J. L. Roberts, I. Houghton
Journal: Thorax (2011)

<h3>Introduction and Aim</h3> A Cochrane review concluded that there is a lack of evidence to support lung function and lung age measures as a method for increasing smoking cessation quit rates. This study aims to assess whether providing lung health checks in workplaces and community settings, combined with immediate access to high quality smoking cessation advice, will promote behaviour change in smokers. <h3>Method</h3> The intervention consisted of spirometry followed by a detailed and personalised explanation of the findings. The results were delivered in plain non-clinical language, using lung age, visual tools and local analogies. The results were augmented by a written report and advice with regard to any action indicated. To capitalise on the tension created by the intervention, current smokers were strongly encouraged to seize the moment and have an immediate discussion with a stop smoking adviser who was positioned within easy reach. The smoking status of every individual tested was recorded, along with their age, gender, test results and action advised. <h3>Results</h3> 1054 smokers have undertaken the lung health check. 953 were given brief advice to stop smoking. 467 (49%) subsequently registered with the stop smoking service. <h3>Conclusions</h3> Regardless of the spirometry result, whether normal or abnormal, a clear understanding of your lung health appeared to be a powerful motivational trigger and teachable moment for behaviour change. This innovative model potentially provides all the ingredients in one location for promoting smoking cessation as described by Robert West in the 3 Ts strategy: Tension, Trigger, Treatment.1 The offer of a lung health check was exceptionally popular in all settings, even among traditionally hard-to-reach groups, and could be targeted according to local need. Joint working with the smoking cessation service improved the outcome for smokers as it took advantage of the immediate situation, triggering the impulse to make a quit attempt. These results justify further work collecting follow-up data to establish whether the trigger of a lung health check converts to a successful long-term quit.
Acute effects of dexamethasone on cation transport in colonic epithelium.
Authors: G I Sandle, F McGlone
Journal: Gut (1987)

Single pharmacological doses of glucocorticoid hormones stimulate net Na+ and water absorption, K+ secretion and electrical potential difference in rat distal colon and human rectum after five hours. To determine the cellular basis of these effects, the Na+ and K+ transport properties of epithelial cell membranes in rat distal colon were studied in vitro five hours after in vivo treatment with dexamethasone 600 micrograms/100 g body weight. Compared with control tissues, dexamethasone increased transepithelial voltage 3.5-fold (p less than 0.001) and short circuit current 4.5-fold (p less than 0.001), and decreased total resistance by 20% (p less than 0.005). Measurements of cell membrane voltages obtained with intracellular microelectrodes indicated that the dexamethasone-induced rise in transepithelial voltage reflected a significant decrease (p less than 0.05) in apical membrane voltage, consistent with the induction of apical Na+ channels and the stimulation of electrogenic Na+ absorption. Apical addition of 10(-4) mol/l amiloride (a Na+ channel blocker) and then 30 mmol/l tetraethylammonium chloride (TEA; a K+ channel blocker) to control tissues had little or no effect on transepithelial electrical parameters, indicating the absence of significant apical Na+ and K+ conductances. In contrast, in dexamethasone treated tissues, amiloride and TEA produced electrical changes that were consistent with the inhibition of glucocorticoid-induced apical Na+ and K+ conductances. Kinetic studies of the basolateral membrane Na+-K+ pump revealed that five hours after administration, dexamethasone had no effect on the maximum capacity of the pump for Na+ transport, but significantly increased the affinity of the pump for Na+, and the number of Na+ ions binding to each pump site. Thus, the acute stimulatory effects of dexamethasone on distal colonic Na+ absorption and K+ secretion reflect increased apical membrane conductance to Na+ and K+, and an increase in the 9efficiency9 of the basolateral membrane Na+-K+ pump.
Improved health-related quality of life following a randomized controlled trial of alefacept treatment in patients with chronic plaque psoriasis
Authors: S.R. Feldman, A. Menter, J.Y. Koo
Journal: British Journal of Dermatology (2004)

Psoriasis has a negative impact on patients' quality of life. Treatment strategies should address both the cutaneous manifestations of the disease and their impact on quality of life.To evaluate the effect of alefacept on quality of life in 553 patients with chronic plaque psoriasis.In this multicentre, double-blind, parallel-groups study, patients were randomized to receive alefacept for two courses, alefacept in course 1 and placebo in course 2, or placebo in course 1 and alefacept in course 2. In each course, alefacept 7.5 mg or placebo was administered once weekly by 30-s intravenous injection for 12 weeks followed by 12 weeks of observation. The Dermatology Life Quality Index (DLQI), Dermatology Quality of Life Scales (DQOLS) and Short Form-36 Health Survey (SF-36) were administered at baseline, 2 weeks after the last dose in both courses, at the beginning of course 2, and at the end of the observation period in both courses.In course 1, alefacept significantly reduced (improved) mean DLQI scores compared with placebo: 4.4 vs. 1.8 at 2 weeks after the last dose (P<0.0001) and 3.4 vs. 1.4 at 12 weeks after the last dose (P<0.001). Patients who received two courses of alefacept experienced additional enhancement of quality of life measures during the second course. Similar results were observed for the DQOLS. The SF-36 survey confirmed that alefacept had no negative impact on general quality of life.Alefacept improved quality of life in patients with chronic plaque psoriasis and maintained this benefit for at least 12 weeks following cessation of treatment. A second course of alefacept provided additional quality of life benefit.
Causes and outcome in cough
Authors: Danai Karamanou, S. Bean, Mahesh Prabhu, Hannah Walden, Stephen Clark, Paul Corris, John Dark, Andrew Fisher
Journal: Thorax (2009)

Methods 89 subjects with physician-diagnosed asthma were studied (mean age 57.4 (¡12.0)years; 57.3% female; 7.9% smokers; 39.3% ex-/52.8%non-smokers; median asthma duration 29.0 years (10.0-68.0);mean forced expiratory volume in 1 s (FEV 1 ) % predicted 86.4% (¡22.1);median dose response ratio (DRR) to methacholine 24.5 (0.0-1970.1); median inhaled corticosteroid (ICS) dose 800.0 mg (0.0-4000.0); median sputum eosinophils 2.0% (0.0-26.0)).Subjects underwent 24-hour ambulatory cough monitoring with the VitaloJak cough monitor; coughs were manually counted and expressed as number of explosive cough sounds per hour (cs/h).In addition, subjects completed the Juniper Asthma Control Questionnaire (ACQ) and underwent sputum induction.Results Cough recordings were obtained in 96.6% and sputum samples in 61.8% of subjects.Median cough rates were higher by day (3.7 cs/h (0.2-41.3)) than by night (0.5 cs/h (0.0-29.6)) (p,0.001) and median ACQ score was 1 (range 0-4.4).Objective cough rates correlated with ACQ scores by day (r = 0.28; p = 0.008), night (r = 0.24; p = 0.027) and over 24 h (r = 0.33; p = 0.003).However, there were no significant correlations between cough rates and either sputum eosinophils (%: r = 0.16; p = 0.26; cells 610 6 /g sputum: r = 0.14; p = 0.31) or neutrophils (%: r = 20.09;p = 0.50; cells 610 6 /g sputum: r = 20.06;p = 0.66).Similarly there were no significant correlations between ACQ scores and sputum eosinophils (%: r = 0.20; p = 0.15; cells 610 6 /g sputum: r = 0.26; p = 0.054) and neutrophils (%: r = 0.02; p = 0.90; cells 610 6 /g sputum: r = 0.07; p = 0.61).In a linear regression model, the percentage of eosinophils (p = 0.005), smoking pack year history (p = 0.005) and overall cough rate (p = 0.008) explained 38% of the variance in ACQ scores (p,0.001;adjusted R 2 ).In a similar regression model, eosinophils 610 6 /g sputum (p,0.001),smoking pack year history (p = 0.005) and overall cough rate (p = 0.002) explained 47.9% of the variance in ACQ scores (p,0.001).Conclusions Higher cough rates indicate poor asthma control.Sputum eosinophils, 24 h cough rate and smoking history independently predict asthma control, and number of eosinophils corrected for sputum weight explains more of the variance in ACQ scores than percentage eosinophils. S25
Development of chronic myelocytic leukemia during the course of acute lymphocytic leukemia in an adult
Authors: Barry L. Fisher, Roger M. Lyons, David A. Sears
Journal: American Journal of Hematology (1977)

A 59-year-old patient is described who presented with acute lymphocytic leukemia. Complete remission was induced rapidly with vincristine and prednisone. Nine months later he acquired the clinical and hematological picture of a myeloproliferative disease, and bone marrow cytogenetic studies demonstrated the presence of the Philadelphia chromosome. Within 4 months he again developed overt acute lymphocytic leukemia and died. Several lines of evidence have recently indicated a relationship between myeloproliferative and lymphoproliferative disorders, particularly chronic myelocytic and acute lymphocytic leukemia. This patient's course is another example of that association.
In Vivo Evidence for Low Striatal Vesicular Monoamine Transporter 2 (VMAT2) Availability in Cocaine Abusers
Authors: Rajesh Narendran, Brian J. Lopresti, Diana Martinez, Neale Scott Mason, Michael Himes, Maureen A. May, Dennis C. Daley, Julie C. Price, Chester A. Mathis, W. Gordon Frankle
Journal: American Journal of Psychiatry (2011)

Objective: Positron emission tomography (PET) imaging studies in cocaine abusers have shown that low dopamine release in the striatum following an amphetamine challenge is associated with higher relapse rates. One possible mechanism that might lead to lower amphetamine-induced dopamine release is low availability of dopamine storage vesicles in the presynaptic terminals for release. Consistent with this hypothesis, postmortem studies have shown low levels of vesicular monoamine transporter, type 2 (VMAT2), the membrane protein that regulates the size of the vesicular dopamine pool, in cocaine abusers relative to healthy subjects. To confirm the postmortem findings, the authors used PET and the VMAT2 radioligand [11C]-(+)-dihydrotetrabenazine (DTBZ) to assess the in vivo VMAT2 availability in a group of 12 recently abstinent cocaine-dependent subjects and matched healthy comparison subjects. Method: [11C]DTBZ nondisplaceable binding potential (BPND) was measured by kinetic analysis using the arterial input function or, if arterial input was unavailable, by the simplified reference tissue method. Results: [11C]DTBZ BPND was significantly lower in the cocaine abusers than in the comparison subjects in the limbic striatum (10.0% lower), associative striatum (–13.4%), and sensorimotor striatum (–11.5%). Conclusions: The results of this in vivo PET study confirm previous in vitro reports of low VMAT2 availability in the striatum of cocaine abusers. It also suggests a compensatory down-regulation of the dopamine storage vesicles in response to chronic cocaine abuse and/or a loss of dopaminergic terminals. Further research is necessary to understand the clinical relevance of this observation to relapse and outcome in abstinent cocaine abusers.
Neurodevelopmental Outcomes at 4 to 8 Years of Children Born at 22 to 25 Weeks’ Gestational Age
Authors: Gregory P. Moore, Brigitte Lemyre, Nick Barrowman, Thierry Daboval
Journal: JAMA Pediatrics (2013)

Many centers delivering infants at 22 to 25 weeks' gestation have limited data regarding their outcomes. A meta-analysis of the 4- to 8-year neurodevelopmental outcomes and exploration of the limitations of meta-analysis would aid physicians and parents to plan care for these infants.To determine the rate of moderate to severe and severe neurodevelopmental impairment by gestational age in extremely preterm survivors followed up between ages 4 and 8 years, as well as to determine whether there is a significant difference in impairment rates between the successive weeks of gestation of survivors.A peer-reviewed search strategy obtained English-language publications from MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, and EMBASE. Personal files and reference lists from identified articles were searched. Contemporary cohorts were obtained by restriction to those published after 2004. Inclusion criteria were prospective cohort studies, follow-up rate of 65% or more, use of standardized testing or classification for impairment, reporting by gestation, and meeting prespecified definitions of impairment. We excluded randomized clinical trials, highly selective cohorts, consensus statements, and reviews. Of 1771 identified records, 89 full-text publications were assessed for eligibility. Using the full text of each publication, 2 authors independently followed a 2-step procedure. First, they determined that 9 studies met inclusion criteria. Next, they extracted data using a structured data collection form. Investigators were contacted for data clarification.All extremely preterm infant survivors have a substantial likelihood of developing moderate to severe impairment. Wide confidence intervals at the lower gestations (eg, at 22 weeks, 43% [95% CI, 21%-69%]; heterogeneity I2, 0%) and high heterogeneity at the higher gestations (eg, at 25 weeks, 24% [95% CI, 17%-32%]; I2, 66%) limit the results. There was a statistically significant absolute decrease in moderate to severe impairment between each week of gestation (6.5% [95% CI, 2%-11%]).Knowledge of these data, including the limitations, should facilitate discussion during the shared decision-making process about care plans for these infants, particularly in centers without their own data. More prospective, high-quality, complete cohorts are needed.
Polymyalgia rheumatica and antimitochondrial antibodies.
Authors: M A Sattar, M I Cawley, T J Hamblin, J C Robertson
Journal: Annals of the Rheumatic Diseases (1984)

Antimitochondrial antibodies (AMA) were detected in the sera of 11 of 36 patients with a clinical diagnosis of polymyalgia rheumatica (PMR) in whom comprehensive autoantibody screening had been performed. AMA did not correlate with biochemical changes of hepatic dysfunction, which are common in PMR, nor with parameters of musculoskeletal inflammation. Possible explanations are discussed.
Bullous pemphigoid in pregnancy: contrasting behaviour in two patients.
Authors: B.C. Gee, J. Allen, N.P. Khumalo, F. Wojnarowska
Journal: British Journal of Dermatology (2001)

Bullous pemphigoid (BP) is an increasingly common immunobullous disease of the elderly, and, due to the late age of onset, is rarely seen in women of fertile age. Consequently, to the best of our knowledge no cases of BP in pregnancy have been described. We present two cases of BP that have differed in disease behaviour during pregnancy.
S1P3-mediated cardiac fibrosis in sphingosine kinase 1 transgenic mice involves reactive oxygen species
Authors: Noriko Takuwa, Sei-Ichiro Ohkura, Shin-Ichiro Takashima, Keisuke Ohtani, Yasuo Okamoto, Tamotsu Tanaka, Kaoru Hirano, Soichiro Usui, Fei Wang, Wa Du, Kazuaki Yoshioka, Yoshiko Banno, Motoko Sasaki, Ikuyo Ichi, Miwa Okamura, Naotoshi Sugimoto, Kiyomi Mizugishi, Yasuni Nakanuma, Isao Ishii, Masayuki Takamura, Shuichi Kaneko, Shosuke Kojo, Kiyoshi Satouchi, Kunitoshi Mitumori, Jerold Chun, Yoh Takuwa
Journal: Cardiovascular Research (2009)

Sphingosine kinase 1 (SPHK1), its product sphingosine-1-phosphate (S1P), and S1P receptor subtypes have been suggested to play protective roles for cardiomyocytes in animal models of ischaemic preconditioning and cardiac ischaemia/reperfusion injury. To get more insight into roles for SPHK1 in vivo, we have generated SPHK1-transgenic (TG) mice and analysed the cardiac phenotype.SPHK1-TG mice overexpressed SPHK1 in diverse tissues, with a nearly 20-fold increase in enzymatic activity. The TG mice grew normally with normal blood chemistry, cell counts, heart rate, and blood pressure. Unexpectedly, TG mice with high but not low expression levels of SPHK1 developed progressive myocardial degeneration and fibrosis, with upregulation of embryonic genes, elevated RhoA and Rac1 activity, stimulation of Smad3 phosphorylation, and increased levels of oxidative stress markers. Treatment of juvenile TG mice with pitavastatin, an established inhibitor of the Rho family G proteins, or deletion of S1P3, a major myocardial S1P receptor subtype that couples to Rho GTPases and transactivates Smad signalling, both inhibited cardiac fibrosis with concomitant inhibition of SPHK1-dependent Smad-3 phosphorylation. In addition, the anti-oxidant N-2-mercaptopropyonylglycine, which reduces reactive oxygen species (ROS), also inhibited cardiac fibrosis. In in vivo ischaemia/reperfusion injury, the size of myocardial infarct was 30% decreased in SPHK1-TG mice compared with wild-type mice.These results suggest that chronic activation of SPHK1-S1P signalling results in both pathological cardiac remodelling through ROS mediated by S1P3 and favourable cardioprotective effects.
Chronic parvovirus B19 infection and systemic necrotising vasculitis: opportunistic infection or aetiological agent?
Authors: T.H. Finkel, D.Y.M. Leung, R.J. Harbeck, E.W. Gelfand, T.J. Török, S.R. Zaki, Lj Anderson, P.J. Ferguson, F.T. Saulsbury, E.L. Durigon, J.R. Hollister
Journal: The Lancet (1994)
Serum complement in chronic liver disease
Authors: B. J. Potter, A. M. Trueman, E. A. Jones
Journal: Gut (1973)

Total serum haemolytic complement activity (CH(50)) and the serum concentrations of both the third and fourth components of the complement system (C3 and C4) have been measured in 29 control subjects, 92 patients with chronic hepatocellular disease, and eight patients with large duct biliary tract obstruction. The mean C4 concentration was reduced in all types of chronic liver disease studied. However, the mean CH(50) and C3 values were increased in compensated primary biliary cirrhosis, were relatively normal in non-cirrhotic chronic active hepatitis, and were decreased in cryptogenic cirrhosis, particularly when ascites was present. There was a significant correlation between CH(50) and C3 in patients with chronic liver disease but no correlation between CH(50) and C4 or between C3 and C4. Raised values for CH(50) and C3 in primary biliary cirrhosis may be due at least in part to concomitant cholestasis since these values tend to be raised in patients with large duct biliary tract obstruction. Although primary biliary cirrhosis, chronic active hepatitis, and cryptogenic cirrhosis are considered to be part of a spectrum of chronic liver disease associated with disturbed immunity, the results of this study emphasize that there are clearly definable differences between these diseases in terms of the pattern of changes in serum complement.