tbuckley/cabot-search huggingface dataset:
Retrospective cohort study of adult cystic fibrosis patients colonised with achromobacter Xylosoxidans
Authors: Jonathan Robson, Christine Etherington, Daniel Peckham
Journal: European Respiratory Journal (2013)

Introduction and Objectives:

Achromobacter Xylosoxidans is an emerging pathogen increasingly being isolated from respiratory samples of cystic fibrosis (CF) patients. The clinical significance of this is uncertain. Our aim was to assess its impact on lung function and exacerbation rate in adult patients with Cystic Fibrosis.

Methods:

We carried out an analysis of those individuals attending the Leeds Cystic Fibrosis Unit who became colonised with A. Xylosoxidans between 2009 and 2011. We recorded spirometric variables, body mass index (BMI), sputum microbiology, and antibiotic prescriptions over the 12 month period before and after first isolation.

Results:

We identified 10 individuals (median age 26 years, 4 male). Median FEV1 was 49% predicted at first isolation and BMI was 20.6. Three patients had nutritional support via PEG or long term NG feeding. One patient was chronically colonised with P. Aeruginosa , and four others had intermittent growth. Six patients were colonised with S. Aureus . None had grown B. Cepacia Complex .

In our cohort there was no decline in FEV1 over the study period. The exacerbation rate measured by prescription of antibiotics did increase following first isolation of A. Xylosoxidans (see table).

View this table:

Results





Conclusion:

We were unable to show any decline in lung function following colonisation with A. Xylosoxidans . Our results do suggest an increased exacerbation rate, and this is likely to affect lung function in the long term. It may be that prompt antibiotic treatment for exacerbations in these patients can prevent lung function decline.
Cetuximab-Activated Natural Killer and Dendritic Cells Collaborate to Trigger Tumor Antigen–Specific T-cell Immunity in Head and Neck Cancer Patients
Authors: Raghvendra M. Srivastava, Steve C. Lee, Pedro A. Andrade Filho, Christopher A. Lord, Hyun-Bae Jie, H. Carter Davidson, Andrés López-Albaitero, Sandra P. Gibson, William E. Gooding, Soldano Ferrone, Robert L. Ferris
Journal: Clinical Cancer Research (2013)

Tumor antigen-specific monoclonal antibodies (mAb) block oncogenic signaling and induce Fcγ receptor (FcγR)-mediated cytotoxicity. However, the role of CD8(+) CTL and FcγR in initiating innate and adaptive immune responses in mAb-treated human patients with cancer is still emerging.FcγRIIIa codon 158 polymorphism was correlated with survival in 107 cetuximab-treated patients with head and neck cancer (HNC). Flow cytometry was carried out to quantify EGF receptor (EGFR)-specific T cells in cetuximab-treated patients with HNC. The effect of cetuximab on natural killer (NK) cell, dendritic cell (DC), and T-cell activation was measured using IFN-γ release assays and flow cytometry.FcγRIIIa polymorphism did not predict clinical outcome in cetuximab-treated patients with HNC; however, elevated circulating EGFR(853-861)-specific CD8(+) T cells were found in cetuximab-treated patients with HNC (P < 0.005). Cetuximab promoted EGFR-specific cellular immunity through the interaction of EGFR(+) tumor cells and FcγRIIIa on NK cells but not on the polymorphism per se. Cetuximab-activated NK cells induced IFN-γ-dependent expression of DC maturation markers, antigen processing machinery components such as TAP-1/2 and T-helper cell (T(H)1) chemokines through NKG2D/MICA binding. Cetuximab initiated adaptive immune responses via NK cell-induced DC maturation, which enhanced cross-presentation to CTL specific for EGFR as well as another tumor antigen, MAGE-3.Cetuximab-activated NK cells promote DC maturation and CD8(+) T-cell priming, leading to tumor antigen spreading and TH1 cytokine release through "NK-DC cross-talk." FcγRIIIa polymorphism did not predict clinical response to cetuximab but was necessary for NK-DC interaction and mAb-induced cross-presentation. EGFR-specific T cells in cetuximab-treated patients with HNC may contribute to clinical response.
2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease
Authors: Robert O. Bonow, Blase A. Carabello, Kanu Chatterjee, Antonio C. de Leon, David P. Faxon, Michael D. Freed, William H. Gaasch, Bruce W. Lytle, Rick A. Nishimura, Patrick T. O'Gara, Robert A. O'Rourke, Catherine M. Otto, Pravin M. Shah, Jack S. Shanewise
Journal: Circulation (2008)
Reduced exertional dyspnea with supplemental oxygen in patients with COPD - Characteristics of responders and non-responders
Authors: Nina Faksvåg Caspersen, Christine Gudim Karlsen, Anne Edvardsen, Siri Skumlien
Journal: European Respiratory Journal (2012)

Introduction: Ambulatory oxygen is recommended for COPD patients who desaturate during activity, and who experience subjective effect of oxygen supplement. COPD patients with no former oxygen treatment admitted for rehabilitation were referred to extended testing if oxygen saturation measured by pulse oximetry (SpO2) during 6-minute walk test (6MWT) fell below 88%.  Aim: Our study aimed at identifying characteristics that differed between patients who experienced subjective effect of oxygen during constant load treadmill test and those who did not.  Methods: Lung function was measured and expressed in % of reference values. Two 5 min constant load treadmill tests were performed at a speed just below 6MWT to mimic walking speed in daily activity. Arterial bloodgas samples were drawn before stop. Dyspnea was measured on Borg CR10 scale. Blinded and in random order, patients received oxygen supplement 6 L/min or placebo air administered continously through nasual catheter.  Results: 27 of 39 patients rated their dyspnoea at least 1 Borg unit lower with oxygen than without. There were no differences in age (64 (8); 65 (6) p=0,56), FEV1 (37 (15); 32 (16) p=0,33), RV (193 (74), 171 (88) p=0,46), TLC (115 (40), 107 (49) p=0,66), DLCOVA (38 (15); 37 (23) p=0,94), resting pO2 (kPa)(8,9 (0,6); 8,8 (0,9) p=0,92), nadir pO2 with placebo (6,8 (0,4); 6,5 (0,8) p=0,19), nadir SpO2 during 6MWT (81(3); 78(5) p=0,10) or pO2 with oxygen (kPa)(10,4 (1,3); 10,9 (1,8), p=0,19) between patients with subjective effect and those without.  Conclusion: None of the registered variables were helpful in predicting subjective effect of ambulatory oxygen.
Cardiovascular effects of a non-xanthine-selective antagonist of the A1 adenosine receptor in the anaesthetised pig: pharmacological and therapeutic implications
Authors: A. Sidi, R. Wesley, R. Barrett, W. Rush, L. Belardinelli
Journal: Cardiovascular Research (1994)

Objective: To study antagonism of A1 adenosine receptors in an anaesthetised open chest swine model, the selective A1 receptor antagonist, N6-endonorbornan-2-yl-9-methyladenine (N-0861), was examined to see if it attenuates bradycardia, augments reflex tachycardia associated with adenosine infusion, or both. Its effects were compared with those of the non-selective antagonist of adenosine A1 and A2 receptors, 8-(p-sulphophenyl)- theophylline (8-pST). Methods: Twenty nine pigs were studied. The prolongation of P-R interval mediated by A1 receptors, the increase in left anterior descending coronary artery blood flow mediated by A2 receptors, and decreases in systemic and left ventricular pressures and first derivative of left ventricular pressure (dP/dt) were monitored in each animal assigned to one of three protocols. (1) Adenosine, 40 to 180 (μg·kg−1·min−1, was infused for more than 6 min before and immediately after rapid infusion of 8-pST, 5 mg·kg−1 intravenously, or a solvent that did or did not contain N-0861, 0.2 mg·kg−1 intravenously (n = 14). (2) In the same animal, we compared N-0861 and 8-pST in reversing responses mediated by A1 and A2 receptors during two 10 min infusions of adenosine separated by a 1 h washout period (n = 7). (3) N-0861 with adenosine (mean dose, 0.4 mg·kg−1) was infused with or without complete autonomic blockade with atropine (2.5 mg·kg−1) and propranolol (2 mg·kg−1) (n = 8). Results: Adenosine prolonged P-R interval (and cycle length in non-paced hearts), increased coronary flow, and decreased calculated coronary resistance. N-0861 alone did not affect any variable, but N-0861 with adenosine prevented or reversed A1 receptor mediated prolongation of P-R interval in paced hearts and cycle length in non-paced hearts and enhanced A2 receptor mediated coronary vasodilatation. Left ventricular dP/dt and rate-pressure product were maintained with N-0861 and adenosine, and N-0861 unmasked a postadenosine reflex tachycardia. Prolonged PR interval, decreased heart rate, and increased coronary flow were prevented or reversed by the non-selective antagonist 8-pST. Conclusions: Selectivity of N-0861 for the adenosine A1 receptor may, without reducing coronary blood flow, ameliorate bradyarrhythmia and maintain the positive inotropic response when exogenous adenosine is given or when interstitial myocardial adenosine is increased. Cardiovascular Research 1994;28:621-628
Healthy cookery lessons still affect eating habits six months later, Australian study finds
Authors: J. Wise
Journal: BMJ (2014)

A community based cooking skills programme backed by the celebrity chef Jamie Oliver has been shown to bring about small but sustained improvements in healthy eating behaviour.

The study, which looked at Jamie’s Ministry of Food Australia programme, found over time that participants spent less on fast food and more on fruit and vegetables, felt more confident about cooking healthy meals, and were more likely to eat meals at a dinner table as a family. …
Quality indicators in rheumatology: valid for whom?
Authors: T. P M Vliet Vlieland, T. W J Huizinga
Journal: Annals of the Rheumatic Diseases (2009)

BMJ Careers online has re-launched to give you an even better online experience.You'll still find our online services such as jobs, courses and careers advice, but now they're even easier to navigate and quicker to find. New features include:c Job alerts -you tell us how often you want to hear from us with either daily or weekly alerts c Refined keyword searching making it easier to find exactly what you want c Contextual display -when you search for articles or courses we'll automatically display job adverts relevant to your search c Recruiter logos linked directly to their organisation homepage -find out more about the company before you apply c RSS feeds now even easier to set up Visit careers.bmj.com to find out more.
Effects of α1-Acid Glycoprotein on the Clinical Pharmacokinetics of 7-Hydroxystaurosporine
Authors: Alex Sparreboom, Huachen Chen, Milin R. Acharya, Adrian M. Senderowicz, Richard A. Messmann, Takashi Kuwabara, David J. Venzon, Anthony J. Murgo, Donna Headlee, Edward A. Sausville, William D. Figg
Journal: Clinical Cancer Research (2004)

Abstract Objective: UCN-01 (7-hydroxystaurosporine) is a small molecule cyclin-dependent kinase modulator currently under clinical development as an anticancer agent. In vitro studies have demonstrated that UCN-01 is strongly bound to the acute-phase reactant α 1-acid glycoprotein (AAG). Here, we examined the role of protein binding as a determinant of the pharmacokinetic behavior of UCN-01 in patients. Experimental Design: Pharmacokinetic data were obtained from a group of 41 patients with cancer receiving UCN-01 as a 72-hour i.v. infusion (dose, 3.6 to 53 mg/m2/day). Results: Over the tested dose range, total drug clearance was distinctly nonlinear (P = 0.0076) and increased exponentially from 4.33 mL/hour (at 3.6 mg/m2/day) to 24.1 mL/hour (at 54 mg/m2/day). As individual values for AAG increased, values for clearance decreased in a linear fashion (R2 = 0.264; P = 0.0008), although the relationship was shallow, and the data showed considerable scatter. Interestingly, no nonlinearity in the unbound concentration (P = 0.083) or fraction at the peak plasma concentration of UCN-01 was apparent (P = 0.744). Conclusion: The results suggest the following: (1) that extensive binding to AAG may explain, in part, the unique pharmacokinetic profile of UCN-01 described previously with a small volume of distribution and slow systemic clearance, and (2) that measurement of total UCN-01 concentrations in plasma is a poor surrogate for that of the pharmacologically active fraction unbound drug.
Tonsillar homing of Epstein-Barr virus-specific CD8+ T cells and the virus-host balance
Authors: A. D. Hislop
Journal: Journal of Clinical Investigation (2005)

Patients with infectious mononucleosis (IM) undergoing primary EBV infection show large expansions of EBV-specific CD8+ T cells in the blood. While latent infection of the B cell pool is quickly controlled, virus shedding from lytically infected cells in the oropharynx remains high for several months. We therefore studied how responses localize to the tonsil, a major target site for EBV, during primary infection and persistence. In acute IM, EBV-specific effectors were poorly represented among CD8+ T cells in tonsil compared with blood, coincident with absence of the CCR7 lymphoid homing marker on these highly activated cells. In patients who had recently recovered from IM, latent epitope reactivities were quicker than lytic reactivities both to acquire CCR7 and to accumulate in the tonsil, with some of these cells now expressing the CD103 integrin, which mediates retention at mucosal sites. By contrast, in long-term virus carriers in whom both lytic and latent infections had been controlled, there was 2- to 5-fold enrichment of lytic epitope reactivities and 10- to 20-fold enrichment of latent epitope reactivities in tonsil compared with blood; up to 20% of tonsillar CD8+ T cells were EBV specific, and many now expressed CD103. We suggest that efficient control of EBV infection requires appropriate CD8+ T cell homing to oropharyngeal sites.
Treatment of spondyloarthropathies with antibodies against tumour necrosis factor alpha : first clinical and laboratory experiences
Authors: J. Braun
Journal: Annals of the Rheumatic Diseases (2000)

Drug treatment of patients with spondyloarthropathies (SpA), especially ankylosing spondylitis (AS) has limited capacity.1 Pain but not disease activity can be reduced by non-steroidal anti-inflammatory drugs (NSAIDs), in severe cases very high doses are needed.2 By examination of sacroiliac biopsy specimens we have shown that, in correlation to disease activity assessed by magnetic resonance imaging (MRI), T cells and macrophages3 and tumour necrosis factor α (TNFα) mRNA4 and protein (fig 1) but no bacterial DNA5 is present in these joints that are pathognomonically involved in AS.6 Furthermore, anti-TNFα monoclonal antibodies (mAb) have recently been shown to be efficacious in Crohn's disease7—a disease that is strongly linked to AS because more than 60% of AS patients have clinically often silent gut lesions resembling Crohn's colitis.8 Furthermore, in another chronic inflammatory rheumatic disease, rheumatoid arthritis (RA), anti-TNF treatment has proved efficacious and even seems to prevent joint damage.9



Figure 1 
Immunohistological examination of a sacroiliac biopsy specimen obtained by computed tomography guided biopsy of a 23 year old patient with ankylosing spondylitis, four years disease duration, with inflammatory back pain grade 6 on a visual analogue scale (0–10). The red staining indicates a mononuclear cell positive for TNFα (APAAP staining technique).



TNFα is a cytokine that is mainly produced by monocytes and macrophages and to a lesser degree by T cells. There are two specific receptors, a 55 kDa and a 75 kDa present on many cell types. TNFα mediates inflammatory and immunoregulatory activities. Effects on cells such as lymphocyte activation and fibroblast proliferation, on mediators such as other cytokines like interleukin 1(IL1), IL6 and IL8, chemokines, prostaglandins, metalloproteinases, on the vasculature by promoting angiogenesis and on upregulation of adhesion molecules and transendothelial migration of leucocytes are well described. In in vitro and in …
Pacemaker or Defibrillator Surgery without Interruption of Anticoagulation
Authors: David H. Birnie, Jeff S. Healey, George A. Wells, Atul Verma, Anthony S. Tang, Andrew D. Krahn, Christopher S. Simpson, Felix Ayala-Paredes, Benoit Coutu, Tiago L.L. Leiria, Vidal Essebag
Journal: New England Journal of Medicine (2013)

Many patients requiring pacemaker or implantable cardioverter-defibrillator (ICD) surgery are taking warfarin. For patients at high risk for thromboembolic events, guidelines recommend bridging therapy with heparin; however, case series suggest that it may be safe to perform surgery without interrupting warfarin treatment. There have been few results from clinical trials to support the safety and efficacy of this approach.We randomly assigned patients with an annual risk of thromboembolic events of 5% or more to continued warfarin treatment or to bridging therapy with heparin. The primary outcome was clinically significant device-pocket hematoma, which was defined as device-pocket hematoma that necessitated prolonged hospitalization, interruption of anticoagulation therapy, or further surgery (e.g., hematoma evacuation).The data and safety monitoring board recommended termination of the trial after the second prespecified interim analysis. Clinically significant device-pocket hematoma occurred in 12 of 343 patients (3.5%) in the continued-warfarin group, as compared with 54 of 338 (16.0%) in the heparin-bridging group (relative risk, 0.19; 95% confidence interval, 0.10 to 0.36; P<0.001). Major surgical and thromboembolic complications were rare and did not differ significantly between the study groups. They included one episode of cardiac tamponade and one myocardial infarction in the heparin-bridging group and one stroke and one transient ischemic attack in the continued-warfarin group.As compared with bridging therapy with heparin, a strategy of continued warfarin treatment at the time of pacemaker or ICD surgery markedly reduced the incidence of clinically significant device-pocket hematoma. (Funded by the Canadian Institutes of Health Research and the Ministry of Health and Long-Term Care of Ontario; BRUISE CONTROL ClinicalTrials.gov number, NCT00800137.).
Prevention of anterior cruciate ligament injuries in female basketball players in japan: an intervention study over four seasons
Authors: Y Nagano, H Miki, K Tsuda, Y Shimizu, T Fukubayashi
Journal: British Journal of Sports Medicine (2011)

Background Female basketball players are at a higher risk of anterior cruciate ligament (ACL) injury than male players. Therefore, prevention of ACL injury in the former group is essential. Objective To assess the effect of an injury prevention training program on the incidence of ACL injuries in female basketball players. Design Prospective intervention study. Setting Top-level league in Japan. Participants Players from 12 top-league teams. The control season (2006–2007) included 158 players; the first intervention season (2007–2008), 168 players; the second intervention season (2008–2009), 174 players; and the third intervention season (2009–2010), 162 players. Interventions From the middle of the 2007–2008 season, a 3-step injury prevention program was initiated. The program focused on strength, balance, jump-landing techniques, and basketball skills. Subjects were instructed to perform exercises in a neutral position and to avoid lumbar lordosis, rear axial weight bearing, hip adduction, and knee valgus. Main outcome measurements Number and rate of ACL injuries during the four seasons and compliance with the program. Injury incidences were given in terms of per 1000 player-hours (PH). Results Seven non-contact ACL injuries were noted during the control season (0.059/1000 PH); 4, during the first intervention season (0.031/1000 PH); 10, during the second intervention season (0.073/1000 PH); and 2, during the third intervention season (0.016/1000 PH). During the second intervention season, the rate of ACL injuries in the teams that complied with the program was 0.053/1000 PH, while the rate in the teams that did not comply was 0.099/1000 PH. During the third intervention season, the rate of ACL injuries in the teams that complied was 0.011/1000 PH, while the rate in the teams that did not comply was 0.032/1000 PH. Conclusion The results show that the injury prevention program tended to decrease the frequency of ACL injuries.
Microvascular Complications in Childhood-Onset Type 1 Diabetes and Celiac Disease: A Multicenter Longitudinal Analysis of 56,514 Patients From the German-Austrian DPV Database
Authors: Tilman R. Rohrer, Johannes Wolf, Susanne Liptay, Klaus-Peter Zimmer, Elke Fröhlich-Reiterer, Nicole Scheuing, Wolfgang Marg, Martin Stern, Thomas M. Kapellen, Berthold P. Hauffa, Joachim Wölfle, Reinhard W. Holl
Journal: Diabetes Care (2015)

To investigate whether celiac disease (CD) associated with type 1 diabetes increases the risk of microvascular complications.Patients (n = 56,514) aged >10 years with diabetes duration <20 years from 392 centers in Germany and Austria were assigned to one of three categories (n): no CD (50,933), biopsy-confirmed CD (812), or suspected CD (4,769; clinical diagnosis or positive antibodies). The confirmed and suspected groups were combined and analyzed for retinopathy or nephropathy. Cox proportional hazards regression was used to adjust for potential confounders (glycated hemoglobin [HbA1c], age at diabetes onset, sex, smoking, dyslipidemia, and hypertension).Kaplan-Meier analysis revealed that retinopathy and nephropathy occurred earlier in the presence versus absence of CD: retinopathy at age 26.7 years (95% CI 23.7-30.2) in 25% of patients with CD vs. age 33.7 years (33.2-34.4) in 25% without CD and microalbuminuria at age 32.8 years (29.7-42.5) vs. 42.4 years (41.4-43.3). The adjusted risk for both retinopathy (hazard ratio 1.263 [95% CI 1.078-1.481]) and nephropathy (1.359 [1.228-1.504]) was higher in patients with diabetes and CD versus those without CD. Cox regression revealed CD as an independent risk factor for microvascular complications after adjustment for confounders.CD is an independent risk factor for retinopathy and nephropathy in patients with type 1 diabetes. Our study therefore supports the recommendation for regular serologic testing for CD, even in the absence of clinical CD. Further prospective studies are required to investigate whether a gluten-free diet might reduce the risk of microvascular disorders in patients with diabetes and CD.
Aortic valve replacement with Dacron-supported grafts
Authors: D. A. Watson, K. W. Pearson, J. C. Cawley, W. G. Rhea, R. J. Donnelly, F. Dexter
Journal: Thorax (1968)

A method is described for inserting grafts on carrier rings in the aortic area when conditions for free grafting are not applicable, namely, dilated aortic root and friable aortic wall. In addition these grafts are suitable for use in the atrio-ventricular position. The results of 11 cases are presented; one early post-operative death occurred, the follow-up period being 3 to 6 months. It is shown that this method is practicable, the incidence of post-operative aortic incompetence may be reduced, and post-operative gradients do not occur if a valve of sufficient internal diameter is used.
Screening for type 2 diabetes and population mortality over 10 years (ADDITION-Cambridge): a cluster-randomised controlled trial
Authors: Rebecca K Simmons, Justin B Echouffo-Tcheugui, Stephen J Sharp, Lincoln A Sargeant, Kate M Williams, A Toby Prevost, Ann Louise Kinmonth, Nicholas J Wareham, Simon J Griffin
Journal: The Lancet (2012)