tbuckley/cabot-search huggingface dataset:
Mental health effects of varenicline
Authors: M. Harrison-Woolrych
Journal: BMJ (2015)

Results from a new meta-analysis seem at odds with patients’ real life experiences

The safety of drugs for smoking cessation, in particular varenicline (Chantix, Champix; Pfizer) and its effects on mental health, has been debated by regulatory authorities, researchers, prescribers, and patients since varenicline was first marketed nine years ago. The debate is likely to be sharpened by the linked paper by Thomas and colleagues (doi:10.1136/bmj.h1109), a systematic review and meta-analysis of randomised placebo controlled trials that found “no evidence of an increased risk of suicide or attempted suicide, suicidal ideation, depression, or death with varenicline.”1 This finding seems to be at odds with many patients’ experience of psychiatric adverse effects associated with varenicline, recently summarised in a citizen petition to the US Food and Drug Administration (FDA).2 It is timely to assess where the balance of evidence lies so that patients struggling to stop smoking can be advised about the risks of varenicline and consensual decisions about treatment can be made.

Mental health effects of varenicline—including depression, suicidal behaviour, and psychotic reactions—have been reported worldwide3 4 5 6 and are documented on the product information, including a “black box” warning on the Chantix label.7 Since the addition of these warnings in …
Expression of a murine polyclonal T cell receptor marker correlates with the use of specific members of the V beta 8 gene segment subfamily.
Authors: M A Behlke, T J Henkel, S J Anderson, N C Lan, L Hood, V L Braciale, T J Braciale, D Y Loh
Journal: The Journal of Experimental Medicine (1987)

A series of murine T lymphocyte clones were examined for reactivity with the KJ16-133 and F23.1 mAbs. Clones that were KJ16-133+,F23.1+ and KJ16-133-,F23.1+ were identified, but no KJ16-133+,F23.1- clones were observed. Within our panel of clones, therefore, the KJ16-133 antibody identifies a subset of F23.1+ cells. All F23.1+ clones examined express members of the V beta 8 subfamily of beta chain variable region genes; clones expressing V beta 8.1 or V beta 8.2 reacted with both KJ16-133 and F23.1, while clones expressing V beta 8.3 reacted only with F23.1. Thus, the differential reactivity of the KJ16-133 and F23.1 antibodies with cloned T cells correlates with the V beta gene expression of each clone. Reactivity with these antibodies should therefore be of utility for predicting the V beta gene expression in some T cell clones.
Impact of Pathological Characteristics on Local Relapse After Breast-Conserving Therapy: A Subgroup Analysis of the EORTC Boost Versus No Boost Trial
Authors: Heather A. Jones, Ninja Antonini, Augustinus A.M. Hart, Johannes L. Peterse, Jean-Claude Horiot, Françoise Collin, Philip M. Poortmans, S. Bing Oei, Laurence Collette, Henk Struikmans, Walter F. Van den Bogaert, Alain Fourquet, Jos J. Jager, Dominic A.X. Schinagl, Carla C. Wárlám-Rodenhuis, Harry Bartelink
Journal: Journal of Clinical Oncology (2009)

To investigate the long-term impact of pathologic characteristics and an extra boost dose of 16 Gy on local relapse, for stage I and II invasive breast cancer patients treated with breast conserving therapy (BCT).In the European Organisation for Research and Treatment of Cancer boost versus no boost trial, after whole breast irradiation, patients with microscopically complete excision of invasive tumor, were randomly assigned to receive or not an extra boost dose of 16 Gy. For a subset of 1,616 patients central pathology review was performed.The 10-year cumulative risk of local breast cancer relapse as a first event was not significantly influenced if the margin was scored negative, close or positive for invasive tumor or ductal carcinoma in situ according to central pathology review (log-rank P = .45 and P = .57, respectively). In multivariate analysis, high-grade invasive ductal carcinoma was associated with an increased risk of local relapse (P = .026; hazard ratio [HR], 1.67), as was age younger than 50 years (P < .0001; HR, 2.38). The boost dose of 16 Gy significantly reduced the local relapse rate (P = .0006; HR, 0.47). For patients younger than 50 years old and in patients with high grade invasive ductal carcinoma, the boost dose reduced the local relapse from 19.4% to 11.4% (P = .0046; HR, 0.51) and from 18.9% to 8.6% (P = .01; HR, 0.42), respectively.Young age and high-grade invasive ductal cancer were the most important risk factors for local relapse, while margin status had no significant influence. A boost dose of 16 Gy significantly reduced the negative effects of both young age and high-grade invasive cancer.
Antitumor Effect of Intratumoral Administration of Bone Marrow-Derived Dendritic Cells Transduced with Wild-Type <b> <i>p53</i> </b> Gene
Authors: Takayoshi Murakami, Naoyuki Tokunaga, Toshihiko Waku, Shinya Gomi, Shunsuke Kagawa, Noriaki Tanaka, Toshiyoshi Fujiwara
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Dendritic cells (DCs) are attractive effectors for cancer immunotherapy because of their potential to function as professional antigen-presenting cells for initiating cellular immune responses. The tumor suppressor gene p53 is pivotal in the regulation of apoptosis, and ∼50% of human malignancies exhibit mutation and aberrant expression of p53. We investigated the antitumor effect of intratumoral administration of bone marrow-derived dendritic cells transduced with wild-type p53 gene. Experimental Design: We examined whether intratumoral administration of DCs infected with recombinant adenovirus expressing murine wild-type p53 (Ad-mp53) could induce systemic antitumor responses against mutant p53-expressing tumors, highly immunogenic MethA, or weakly immunogenic MCA-207 implanted in syngeneic mice. Results: Accumulation of wild-type p53 protein in bone marrow-derived murine DCs could be successfully achieved by Ad-mp53 infection. Treatment with intratumoral injection of Ad-mp53-transduced DCs caused a marked reduction in the in vivo growth of established MethA and MCA-207 tumors with massive cellular infiltrates. Administration of p53-expressing DCs suppressed the growth of both injected MCA-207 tumors and untreated distant MCA-207 tumors, but not unrelated Lewis lung carcinoma tumors, suggesting the augmentation of systemic immunogenicity against MCA-207 tumor cells. Moreover, intratumoral injection of p53-expressing DCs had a greater antitumor effect than did s.c. immunization. Conclusions: Our results indicate that intratumoral administration of DCs expressing murine wild-type p53 leads to significant systemic immune responses and potent antitumor effects in mutant p53-expressing murine cancer models. These findings raise the possibility of using this strategy of intratumoral injection of p53-expressing DCs for human cancer treatment.
Fatal anaphylaxis after a yellow jacket sting, despite venom immunotherapy, in two patients with mastocytosis
Authors: Joanne N.G. Oude Elberink, Jan G.R. de Monchy, John W. Kors, Jaap J. van Doormaal, Anthony E.J. Dubois
Journal: Journal of Allergy and Clinical Immunology (1997)

J Allergy Clin Immunol 1997;99:153-4.
Ferritin Prevents Calcification and Osteoblastic Differentiation of Vascular Smooth Muscle Cells
Authors: Abolfazl Zarjou, Vikto[Combining Acute Accent]ria Jeney, Paolo Arosio, Maura Poli, Pe[Combining Acute Accent]ter Antal-Szalma[Combining Acute Accent]s, Anupam Agarwal, Gyo[Combining Diaeresis]rgy Balla, Jo[Combining Acute Accent]zsef Balla
Journal: Journal of the American Society of Nephrology (2009)

Vascular calcification plays a role in the pathogenesis of atherosclerosis, diabetes, and chronic kidney disease. Human aortic smooth muscle cells (HSMCs) undergo mineralization in response to elevated levels of inorganic phosphate (Pi) in an active and well-regulated process. This process involves increased activity of alkaline phosphatase and increased expression of core binding factor alpha-1, a bone-specific transcription factor, with the subsequent induction of osteocalcin. Mounting evidence suggests an essential role for the heme oxygenase 1 (HO-1)/ferritin system to maintain homeostasis of vascular function. We examined whether induction of HO-1 and ferritin alters mineralization of HSMCs provoked by high Pi. Upregulation of the HO-1/ferritin system inhibited HSMC calcification and osteoblastic differentiation. Of the products of the system, only ferritin and, to a lesser extent, biliverdin were responsible for the inhibition. Ferritin heavy chain and ceruloplasmin, which both possess ferroxidase activity, inhibited calcification; a site-directed mutant of ferritin heavy chain, which lacked ferroxidase activity, failed to inhibit calcification. In addition, osteoblastic transformation of HSMCs provoked by elevated Pi (assessed by upregulation of core binding factor alpha-1, osteocalcin, and alkaline phosphatase activity) was diminished by ferritin/ferroxidase activity. We conclude that induction of the HO-1/ferritin system prevents Pi-mediated calcification and osteoblastic differentiation of human smooth muscle cells mainly via the ferroxidase activity of ferritin.
When physiology becomes pathology: the role of magnetic resonance imaging in evaluating bone marrow oedema in the humerus in elite tennis players with an upper limb pain syndrome * Commentary
Authors: G Hoy, T Wood, N Phillips, D Connell
Journal: British Journal of Sports Medicine (2006)

Upper limb stresses are well recognised in tennis, and the normal physiological responses of the humerus to externally applied forces are well defined. Changes to both the microscopic and macroscopic bony architecture are often not apparent on plain radiographs in the early stages of a stress reaction. Bone scintigraphy is more sensitive, but not very specific to subtle changes, as is computer aided tomography. Magnetic resonance imaging (MRI) scans are now used to assess many musculoskeletal injuries, and may allow earlier recognition of changes. This study reports on eight high level tennis players (seven professionals, one highly ranked amateur), who all presented during the course of the 2002 Australian Open and its lead up events. All had an upper limb pain syndrome centred around the elbow. Each underwent an MRI scan. A group of asymptomatic players also had scans of the same area to serve as controls. All symptomatic patients had various levels of bone marrow oedema in their distal humerus, some with periosteal reactions, although most without. No scans revealed a cortical breach. The management of these reactions is problematic in players on an international circuit, as review is sporadic and not always coordinated. The timetabling of international tournaments means it is difficult for top players to obtain adequate rest to avoid injury. Awareness of this early overuse reaction needs to be raised to allow preventive and therapeutic options to be considered to reduce the incidence of this humeral stress response producing an upper limb pain syndrome.
Letter: Hiatus hernia and competence of gastro-oesophageal sphincter.
Authors: H D Johnson
Journal: BMJ (1974)

E.B. virus, like other viruses, sometimes does produce lymphomas in animals.I would not be frightened by the prospect of developing infectious mononucleosis after E.B. virus in- oculation and I would discount the danger of developing a Burkitt tumour in the short span of life left to me.The question I would regard as of the utmost importance to me is whether, by E.B. virus inoculation, my tumour could be made once more drugsensitive.The answer to this question is un- known but could, like many another scienti- fic problem, be elucidated by being put to the test.-I am, etc.,
Treatment of Acute Low Pressure Pulmonary Edema in Dogs
Authors: R. M. Prewitt, J. McCarthy, L. D. H. Wood
Journal: Journal of Clinical Investigation (1981)

Severe pulmonary edema sometimes develops despite normal pulmonary capillary wedge pressure (Ppw). The equation describing net transvascular flux of lung liquid predicts decreased edema when hydrostatic pressure is reduced or when colloid osmotic pressure is increased in the pulmonary vessels. We tested these predictions in a model of pulmonary capillary leak produced in 35 dogs by intravenous oleic acid. 1 h later, the dogs were divided into five equal groups and treated for 4 h in different ways: (a) not treated, to serve as the control group (Ppw = 11.1 mm Hg); (b) given albumin to increase colloid osmotic pressure by 5 mm Hg (Ppw = 10.6 mm Hg); (c) ventilated with 10 cm H2O positive end-expiratory pressure (Peep) (transmural Ppw = 10.4 mm Hg); (d) phlebotomized to reduce Ppw to 6 mm Hg; (e) infused with nitroprusside, which also reduced Ppw to 6 mm Hg. Phlebotomy and nitroprusside reduced the edema in excised lungs by 50% (P< 0.001), but Peep and albumin did not affect the edema. Pulmonary shunt decreased on Peep and increased on nitroprusside, and lung compliance was not different among the treatment groups, demonstrating that these variables are poor indicators of changes in edema. Cardiac output decreased during the treatment period in all but the nitroprusside group, where Ppw decreased and cardiac output did not. We conclude that canine oleic acid pulmonary edema is reduced by small reductions in hydrostatic pressure, but not by increased colloid osmotic pressure, because the vascular permeability to liquid and protein is increased. These results suggest that low pressure pulmonary edema may be reduced by seeking the lowest Ppw consistent with adequate cardiac output enhanced by vasoactive agents like nitroprusside. Further, colloid infusions and Peep are not helpful in reducing edema, so they may be used in the lowest amount that provides adequate circulating volume and arterial O2 saturation on nontoxic inspired O2. Until these therapeutic principles receive adequate clinical trial, they provide a rationale for carefully monitored cardiovascular manipulation in treating patients with pulmonary capillary leak.
Regulation of the stem cell marker CD133 is independent of promoter hypermethylation in human epithelial differentiation and cancer
Authors: Davide Pellacani, Richard J Packer, Fiona M Frame, Emma E Oldridge, Paul A Berry, Marie-Christine Labarthe, Michael J Stower, Matthew S Simms, Anne T Collins, Norman J Maitland
Journal: Molecular Cancer (2011)

Epigenetic control is essential for maintenance of tissue hierarchy and correct differentiation. In cancer, this hierarchical structure is altered and epigenetic control deregulated, but the relationship between these two phenomena is still unclear. CD133 is a marker for adult stem cells in various tissues and tumour types. Stem cell specificity is maintained by tight regulation of CD133 expression at both transcriptional and post-translational levels. In this study we investigated the role of epigenetic regulation of CD133 in epithelial differentiation and cancer. DNA methylation analysis of the CD133 promoter was done by pyrosequencing and methylation specific PCR; qRT-PCR was used to measure CD133 expression and chromatin structure was determined by ChIP. Cells were treated with DNA demethylating agents and HDAC inhibitors. All the experiments were carried out in both cell lines and primary samples. We found that CD133 expression is repressed by DNA methylation in the majority of prostate epithelial cell lines examined, where the promoter is heavily CpG hypermethylated, whereas in primary prostate cancer and benign prostatic hyperplasia, low levels of DNA methylation, accompanied by low levels of mRNA, were found. Moreover, differential methylation of CD133 was absent from both benign or malignant CD133+/α2β1integrinhi prostate (stem) cells, when compared to CD133-/α2β1integrinhi (transit amplifying) cells or CD133-/α2β1integrinlow (basal committed) cells, selected from primary epithelial cultures. Condensed chromatin was associated with CD133 downregulation in all of the cell lines, and treatment with HDAC inhibitors resulted in CD133 re-expression in both cell lines and primary samples. CD133 is tightly regulated by DNA methylation only in cell lines, where promoter methylation and gene expression inversely correlate. This highlights the crucial choice of cell model systems when studying epigenetic control in cancer biology and stem cell biology. Significantly, in both benign and malignant prostate primary tissues, regulation of CD133 is independent of DNA methylation, but is under the dynamic control of chromatin condensation. This indicates that CD133 expression is not altered in prostate cancer and it is consistent with an important role for CD133 in the maintenance of the hierarchical cell differentiation patterns in cancer.
Dendrimer-Encapsulated Camptothecins: Increased Solubility, Cellular Uptake, and Cellular Retention Affords Enhanced Anticancer Activity <i>In vitro</i>
Authors: Meredith T. Morgan, Yuka Nakanishi, David J. Kroll, Aaron P. Griset, Michael A. Carnahan, Michel Wathier, Nicholas H. Oberlies, Govindarajan Manikumar, Mansukh C. Wani, Mark W. Grinstaff
Journal: Cancer Research (2006)

Abstract A biocompatible polyester dendrimer composed of the natural metabolites, glycerol and succinic acid, is described for the encapsulation of the antitumor camptothecins, 10-hydroxycamptothecin and 7-butyl-10-aminocamptothecin. The cytotoxicity of the dendrimer-drug complex toward four different human cancer cell lines [human breast adenocarcinoma (MCF-7), colorectal adenocarcinoma (HT-29), non–small cell lung carcinoma (NCI-H460), and glioblastoma (SF-268)] is also reported, and low nmol/L IC50 values are measured. Cellular uptake and efflux measurements in MCF-7 cells show an increase of 16-fold for cellular uptake and an increase in drug retention within the cell when using the dendrimer vehicle. (Cancer Res 2006; 66(24): 11913-21)
Precompetition medical assessment of referees and assistant referees selected for the 2010 FIFA World Cup: Table 1
Authors: Mario Bizzini, Christian Schmied, Astrid Junge, Jiri Dvorak
Journal: British Journal of Sports Medicine (2011)

Several proposals for preparticipation screening to detect risk factors for sudden cardiac death in sports have been published, but referees have been neglected in this respect.A standardised precompetition medical assessment (comprising a general physical, orthopaedic and cardiac examination and blood analysis) was performed in all 90 referees and assistant referees selected for the 2010 Fédération Internationale de Football Association World Cup.More than a third of the referees showed at least one pathological finding in cardiac examinations; however, all follow-up examinations proved to be normal. The relatively high prevalence of pathological findings in the blood analysis and the orthopaedic examination can be attributed to the average age of the referees and none of them was performance limiting.Considering their risk of occult ischaemic heart disease, a precompetition medical assessment including an exercise ECG is recommended in elite male football referees.
Present outlook in bronchiectasis: clinical and social study and review of factors influencing prognosis.
Authors: D A Ellis, P E Thornley, A J Wightman, M Walker, J Chalmers, J W Crofton
Journal: Thorax (1981)

One hundred and sixteen patients with proven bronchiectasis diagnosed at least five years previously were studied to determine the clinical outcome, change in pulmonary function, and degree of social disability. Twenty-two patients had died and the mean duration of follow-up in the survivors was 14 years. The patients who died were characterised by a poorer initial ventilatory capacity than the survivors and cor pulmonale was present in 37% at the time of death. The survivors showed a tendency for improvement in symptoms whether treated surgically or medically. Thirty per cent were better than at diagnosis while only 11% were worse. Measurements of FEV1 and FVC were made at diagnosis and at review, mild airways obstruction being the predominant abnormality. The change in pulmonary function was expressed as the decline in FEV1 in ml/yr. The decline in FEV1 was no greater than expected in 80% of patients and in a further 15% was of the order seen in cigarette smokers with mild airways obstruction. Poor ventilatory capacity was therefore not an important limitation in these patients. Of the survivors 77% had a good work record with less than two weeks loss of work annually from chest illness. The spouses of all married patients were interviewed at home by a trained social worker. Fifty per cent reported no social problem but 46% of spouses found the patient9s cough distasteful and 29% of couples had experienced difficulties with normal sexual life. Seven per cent of the patients were severely disabled. While the overall prognosis of our patients was good a minority still have severe physical and social problems as a result of bronchiectasis.
Modeling the Impact of DNA Methylation on the Evolution of BRCA1 in Mammals
Authors: Gavin A. Huttley
Journal: Molecular Biology and Evolution (2004)

The modified base 5-methylcytosine ((m)C) plays an important functional role in the biology of mammals as an epigenetic modification and appears to exert a striking impact on the molecular evolution of mammal genomes. The collective epigenetic functions of (m)C revolve around its effect on gene transcription, while the influence of this modified base on the evolution of mammal genomes derives from the greatly elevated spontaneous mutation rate of (m)C to T. In mammals, (m)C occurs at the dinucleotides CpG, CpA, and CpT. As a step toward a comprehensive statistical examination of the role of (m)C in mammal molecular evolution, we have developed novel Markov models of codon substitution that incorporate dinucleotide-level terms relevant to (m)C mutation. We apply these models to two data sets of aligned BRCA1 exon 11 sequences from bats and primates. In all cases, terms specific to mutations that affect the dinucleotides CpG, CpA, and CpT significantly improved model fit. For the CpG-specific terms, both transition and transversion substitution rates were elevated. These rates differed between the data sets. Bats exhibited a lower relative rate of substitutions at CpG-containing codons. Transition substitutions were significantly less than 1 at CpA-containing codons but greater than 1 at CpT-containing codons. The inclusion of interaction terms in the codon models to represent possible confounding with the effect of natural selection were supported for codons that contained CpG and CpT, but not CpA. From the results, we infer that mutation of (m)C is a probable factor that affects BRCA1 codons containing the dinucleotide CpG, a possible factor for CpA-containing codons, and an unlikely factor that affects CpT-containing codons. The confounding of estimated terms with the effect of natural selection indicate this confounding must be addressed for comparisons between different coding and noncoding regions.
Epinephrine Autoinjector Use One Year after Training: A Randomised Controlled Comparison of Two Different Devices
Authors: Robert J. Boyle, Annabella Procktor, Matthew Hodes, Jared G. Smith, Claudia Gore, Helen E. Cox, Paul J. Turner, Tom Marrs, Heather Hanna, Katherine Phillips, John O. Warner, Camila Pinto, Thisayanagam Umasunthar
Journal: Journal of Allergy and Clinical Immunology (2015)