tbuckley/cabot-search huggingface dataset:
Importance of Expert Central Review in the Diagnosis of Lymphoid Malignancies in a Regional Cancer Network
Authors: Ian E. Proctor, Christopher McNamara, Manuel Rodriguez-Justo, Peter G. Isaacson, Alan Ramsay
Journal: Journal of Clinical Oncology (2011)

The accurate diagnosis of hematologic malignancies remains a challenging area for histopathologists. In 2003, the North Central London Lymphoma network was established to provide a centralized expert review service for general histopathologists based in peripheral nonspecialist hospitals. By studying samples sent for review, we sought to assess the diagnostic and clinical impact of centralized expert review in lymphoma diagnosis.A total of 1,949 patient samples were subject to expert review between 2003 and 2008. Diagnostic discordance rates were identified after expert review, and the impact on patient management was assessed by a hematologic oncology specialist.An overall discordance rate of 27.3% was identified. Among the 10 most commonly referred lymphoid malignancies, the discordance rate varied between 3.6% and 34.1%. A small but significant number of reactive (n = 17) and malignant (n = 5) discordant diagnoses were also identified. Expert central review resulted in a major change to patient management in 2.1% of patients and prevented delays in treatment in 9.3% of patients. During the 6-year study, the discordance rate improved significantly, decreasing from 32% to 13%. Although centralized review incurred additional costs, these were relatively small compared with the costs associated with treatment.This retrospective study demonstrates the importance of expert central review in the accurate diagnosis and timely management of lymphoid malignancies. Furthermore, it shows that where full centralization of services is not viable, a network comprising nonspecialist hospitals linked to a center providing expert review is a practical alternative to full unification of services at a single location and can help prevent local deskilling.
An Empirically Derived Taxonomy for Personality Diagnosis: Bridging Science and Practice in Conceptualizing Personality
Authors: Drew Westen, Jonathan Shedler, Bekh Bradley, Jared A. DeFife
Journal: American Journal of Psychiatry (2011)

Objective: The authors describe a system for diagnosing personality pathology that is empirically derived, clinically relevant, and practical for day-to-day use. Method: A random national sample of psychiatrists and clinical psychologists (N=1,201) described a randomly selected current patient with any degree of personality dysfunction (from minimal to severe) using the descriptors in the Shedler-Westen Assessment Procedure–II and completed additional research forms. Results: The authors applied factor analysis to identify naturally occurring diagnostic groupings within the patient sample. The analysis yielded 10 clinically coherent personality diagnoses organized into three higher-order clusters: internalizing, externalizing, and borderline-dysregulated. The authors selected the most highly rated descriptors to construct a diagnostic prototype for each personality syndrome. In a second, independent sample, research interviewers and patients' treating clinicians were able to diagnose the personality syndromes with high agreement and minimal comorbidity among diagnoses. Conclusions: The empirically derived personality prototypes described here provide a framework for personality diagnosis that is both empirically based and clinically relevant.
Cascade Effects of Medical Technology
Authors: Richard A. Deyo
Journal: Annual Review of Public Health (2002)

▪ Abstract Cascade effect refers to a process that proceeds in stepwise fashion from an initiating event to a seemingly inevitable conclusion. With regard to medical technology, the term refers to a chain of events initiated by an unnecessary test, an unexpected result, or patient or physician anxiety, which results in ill-advised tests or treatments that may cause avoidable adverse effects and/or morbidity. Examples include discovery of endocrine incidentalomas on head and body scans; irrelevant abnormalities on spinal imaging; tampering with random fluctuations in clinical measures; and unwanted aggressive care at the end of life. Common triggers include failing to understand the likelihood of false-positive results; errors in data interpretation; overestimating benefits or underestimating risks; and low tolerance of ambiguity. Excess capacity and perverse financial incentives may contribute to cascade effects as well. Preventing cascade effects may require better education of physicians and patients; research on the natural history of mild diagnostic abnormalities; achieving optimal capacity in health care systems; and awareness that more is not the same as better.
A decisive role for B cells in priming of allergy and tolerance by preconceptional immunization of the mother
Authors: Christine Happle, Christian Hennig, Jelena Skuljec, Gerd Hoymann, Almut Meyer-Bahlburg, Gesine Hansen
Journal: European Respiratory Journal (2013)

Antigen challenge in early life, even before birth has been shown to crucially influence an individual9s susceptibility to allergy and asthma. In this context, we showed in a murine asthma model that maternal tolerization by mucosal allergen application shortly before pregnancy induces tolerance in the offspring via transfer of immunoglobulins and induction of tolerogenic T cells.  We aimed to further decipher the role of B cells in this context. In an ovalbumin-based murine asthma model, we analyzed the effect of preconceptional maternal tolerization on the offspring9s asthma risk and compared B cell knock out (µMT) versus wild type mice. As shown before, preconceptional maternal tolerization protected the progeny of wild type mice, which showed reduced airway inflammation, BALF cell count, ova-specific IgG, IgE and Th2 cytokines as compared to the offspring of non tolerized controls. In contrast, in B cell knock out mice preconceptional tolerization led to an aggravation of the offspring9s asthmatic phenotype, where higher BALF cell count and stronger lung inflammation, airwayhyper reactivity, and Th2 cytokines occurred. The transfer of B cells into µMT dams before tolerization and mating had a tolerogenic effect in the F1 generation. Furthermore, preconceptional tolerization and cross-mating of µMT and wild-type mice revealed a significant correlation between the offspring9s B cells and immunoglobulins on the one hand and regulatory T cells and tolerance induction on the other hand. In summary, our data show a crucial role for B cells in the maternofetal priming towards allergens.
Selective expression of H-2 (i-region) loci controlling determinants on helper and suppressor T lymphocytes.
Authors: K Okumura, L A Herzenberg, D B Murphy, H O McDevitt, L A Herzenberg
Journal: The Journal of Experimental Medicine (1976)

Data presented here show that locidentify in the I-region of the H-2 gene complex are selectively expressed in different functional T-cell subpopulations. These loci are closely linked (or possibly identical) to loci that control immune responses. They control surface determinants which identify helper and suppressor T lymphocytes. Determinants described here on allotype suppressor T cells (Ts) are found on normal (nonsuppressed) lymphoid cells, but are not found on helper T cells (Th). These determinants are controlled by a locus mapping in the I region of the H-2 complex. In an accompanying publication we show that this locus (Ia-4) marks a new I subregion (I-J) and is expressed only on T cells. Thus Ia-4 determinants idenfity a T-cell subpopulation which includes Ts but not Th. Th also carry identifying surface determinants controlled by loci that map to the H-2 complex, probably within the I region. These determinants are not found on Ts. Data presented also establish that loci in the I region control determinants on Th, but do not conclusively demonstrate that these are the determinants that distinguish Th from Ts. The selective expression of H-2-controlled determinants on Ts and Th suggests that these determinants are directly involved in immunoregulation.
Human Mannose-binding Lectin in Immunity
Authors: Jean-Laurent Casanova, Laurent Abel
Journal: The Journal of Experimental Medicine (2004)

Human mannose-binding lectin (MBL) recognizes a wide range of microorganisms and triggers the most ancient pathway of complement activation. However, ∼5% of individuals lack functional serum MBL and have not been found to be prone to severe infections in prospective studies. These data suggest that human MBL is largely redundant for protective immunity and may even have been subject to counter selection because of a deleterious impact.
(16) Incontinentia pigmenti
Authors: O.M. DOLAN, E.A. BINGHAM, J.R. CORBETT
Journal: British Journal of Dermatology (1992)

Journal Article (16) Incontinentia pigmenti Get access O.M. DOLAN, O.M. DOLAN Royal Belfast Hospital for Sick Children, Belfast Search for other works by this author on: Oxford Academic Google Scholar E.A. BINGHAM, E.A. BINGHAM Royal Belfast Hospital for Sick Children, Belfast Search for other works by this author on: Oxford Academic Google Scholar J.R. CORBETT J.R. CORBETT Royal Belfast Hospital for Sick Children, Belfast Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 127, Issue s40, 1 July 1992, Pages 56–57, https://doi.org/10.1111/j.1365-2133.1992.tb01241.x Published: 01 July 1992
Extracellular Matrix Metalloproteinase Inducer Regulates Matrix Metalloproteinase Activity in Cardiovascular Cells
Authors: Roland Schmidt, Andreas Bültmann, Martin Ungerer, Nader Joghetaei, Özgür Bülbül, Sven Thieme, Triantafyllos Chavakis, Bryan P. Toole, Meinrad Gawaz, Albert Schömig, Andreas E. May
Journal: Circulation (2006)

Background— Matrix metalloproteinases (MMPs) are thought to promote progression of atherosclerosis and cardiovascular complications such as plaque rupture. It has been suggested that, on tumor cells, the extracellular MMP inducer (EMMPRIN) is involved in MMP synthesis by as yet unknown mechanisms. On cardiovascular cells, regulation of EMMPRIN in vivo or any functional relevance for MMP induction in vitro has not yet been studied. Thus, we studied EMMPRIN expression on monocytes in acute myocardial infarction (MI) and its potential relevance for MMP activation. Methods and Results— In 20 patients with acute MI, surface expression of EMMPRIN was significantly enhanced on monocytes compared with in 20 patients with chronic stable angina. EMMPRIN upregulation was associated with increased expression of the membrane type 1 MMP (MT1-MMP) on monocytes (flow cytometry) as well as MMP-9 activity (gelatin zymography) in the plasma. At 6 months after successful revascularization, EMMPRIN, MT1-MMP, and MMP-9 had normalized. The secretion of MMP-9 by monocytes was induced by monocyte adhesion to immobilized recombinant EMMPRIN or to EMMPRIN-transfected Chinese hamster ovary cells. Moreover, adherent EMMPRIN-transfected monocytic cells stimulated MMP-2 activity of human vascular smooth muscle cells. Gene silencing of EMMPRIN by small-interfering RNA hindered lipopolysaccharide-induced monocyte secretion of MMP-9, indicating a predominant role of EMMPRIN in MMP-9 induction. Conclusions— EMMPRIN and MT1-MMP are upregulated on monocytes in acute MI. During cellular interactions, EMMPRIN stimulates MMP-9 in monocytes and MMP-2 in smooth muscle cells, indicating that EMMPRIN may display a key regulatory role for MMP activity in cardiovascular pathologies.
Trials in rheumatoid arthritis: choosing the right outcome measure when minimal disease is achievable
Authors: D. T Felson, B. Zhang, J. N Siegel
Journal: Annals of the Rheumatic Diseases (2007)

Exciting advances in rheumatoid arthritis therapy have improved the prospects for patients to live for many years with minimal, if any, detectable disease activity. Recent trials have not only provided evidence on specific medications that might be used to improve outcome but also on therapeutic strategies that might optimise that outcome.

Obviously, the elimination of disease activity is the goal of treating patients with rheumatoid arthritis (RA), or any rheumatic disease. The goal of this editorial is not to question this ultimate aim of treatment or to discuss the design of new treatment strategies or the promise of specific treatments. We propose rather a discussion of how best to measure outcomes in RA trials to optimise our likelihood of achieving this aim of low disease activity at a time when low disease activity is an attainable goal for many patients.

Since they are clinically achievable goals, one reasonable approach to trial outcome measurement in RA might be to focus on low disease activity and, as much as possible, on remission or cure. As suggested by a recent editorial, “Successful therapeutic strategies of the next decade will be measured by the percentage of patients able to achieve remission or at least achieve a very low disease activity state and not by how many patients improved by a certain amount”.1 We shall contend that RA trial outcomes should not focus on remission or even low disease activity, but rather on outcomes that optimise the detection of treatment efficacy. This depends not just on the rate of remission (or low disease activity) in the active treatment group, but on the difference in rates between the treatments being compared. If low disease activity is used as a primary endpoint in a trial in which low disease activity is not attained more often with …
Diagnosis of cystic fibrosis related diabetes: a selective approach in performing the oral glucose tolerance test based on a combination of clinical and biochemical criteria
Authors: B. Yung, M. Kemp, J. Hooper, M. E Hodson
Journal: Thorax (1999)

Cystic fibrosis related diabetes (CFRD) has become increasingly common with the increasing longevity of patients with cystic fibrosis. The diagnosis of CFRD is important as its development may lead to a clinical deterioration which may be reversed with treatment. The oral glucose tolerance test (OGTT) is the method of choice in the diagnosis of CFRD, but performing OGTTs on all patients is inconvenient for patients and labour intensive for staff. The aim of this study was to identify a more selective approach in performing OGTTs in the diagnosis of CFRD based on the use of a combination of clinical and biochemical criteria.Clinically stable adult patients with cystic fibrosis not known to be diabetic attending the Royal Brompton Hospital Cystic Fibrosis Clinic for their annual review were invited to return within a month to have an OGTT. The result of the OGTT was compared with the results of tests performed during the annual review. The sensitivities and specificities of various methods used in the screening or diagnosis of CFRD were determined using OGTT as the "gold standard" diagnostic method. The combination of clinical and biochemical criteria which resulted in the highest sensitivity and specificity in the diagnosis of CFRD was determined.Between August 1996 and May 1997 122 patients became eligible for the study, 91 of whom agreed to take part. The number of patients with normal, impaired, and diabetic glucose tolerance was 58 (64%), 21 (23%), and 12 (13%), respectively. When used alone, abnormal glycosylated haemoglobin (HbA1c) was found to have the highest sensitivity (83%; 95% CI 62 to 100) in the diagnosis of CFRD. The combination of an abnormal random blood glucose and/or abnormal HbA1c and/or symptoms of hyperglycaemia or weight loss was found to have the highest sensitivity (92%; 95% CI 76 to 100) in the diagnosis of CFRD. The specificity of this combination in the diagnosis of CFRD was 79% (95% CI 70 to 88). By selectively performing OGTTs in patients with one or more of the criteria cited above, 11 of the 12 patients with OGTT defined diabetes would have been identified.Patients with cystic fibrosis already have to undergo a large number of routine investigations. The selective approach in performing OGTTs described here has the potential to identify the majority of patients with CFRD without the need to perform this investigation on all patients. This approach is likely to be welcomed by patients and will lead to significant savings in terms of time and resources for patients and staff. Further larger studies are warranted to validate this selective approach in the diagnosis of CFRD.
Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity
Authors: Prasad S. Adusumilli, Leonid Cherkassky, Jonathan Villena-Vargas, Christos Colovos, Elliot Servais, Jason Plotkin, David R. Jones, Michel Sadelain
Journal: Science Translational Medicine (2014)

Regional CAR T cell delivery provides superior protection compared to systemic administration.
Pharmaceutical formulations of anthralin
Authors: M. WHITEFIELD
Journal: British Journal of Dermatology (1981)

Journal Article Pharmaceutical formulations of anthralin Get access M. WHITEFIELD M. WHITEFIELD Dermal Laboratories Limited, Hitchin, Herts Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 105, Issue s20, 1 August 1981, Pages 28–32, https://doi.org/10.1111/j.1365-2133.1981.tb00995.x Published: 01 August 1981
The Victorian Active Script Programme: promising signs for general practitioners, population health, and the promotion of physical activity
Authors: J Sims, N Huang, J Pietsch, L Naccarella
Journal: British Journal of Sports Medicine (2004)

Background: The Active Script Programme (ASP) aimed to increase the number of general practitioners (GPs) in Victoria, Australia who deliver appropriate, consistent, and effective advice on physical activity to patients. To maximise GP participation, a capacity building strategy within Divisions of General Practice (DGPs) was used. The objectives of the programme were to ( a ) train and support GPs in advising sedentary patients, and ( b ) develop tools and resources to assist GPs. Objective: To evaluate the effectiveness of the ASP. Methods: A systems approach was used to promote capacity in Victorian general practice. Economic analyses were incorporated into the programme’s evaluation. Participants were selected DGPs and their GP members. The programme worked with DGPs to train GPs and provide relevant resources. The main outcome measures were ( a ) changes in GP knowledge and behaviour and ( b ) cost effectiveness, based on modelled estimates of numbers of patients advised and adopting physical activity and gaining the associated health benefits. Results: GP awareness and provision of physical activity advice increased. Although the programme’s reach was modest, based on actual GP involvement, the cost effectiveness figures ($138 per patient to become sufficiently active to gain health benefits, and $3647 per disability adjusted life year saved) are persuasive. Conclusions: The ASP increased DGPs’ capacity to support GPs to promote physical activity. There is a strong economic argument for governments to invest in such programmes. However, caution is warranted about the maintenance of patients’ activity levels. Programme refinement to encourage GPs to use community supports more effectively will guide future development. Further research on long term patient adherence through a multisectorial approach is warranted.
Lung function of healthy boys and girls in Jamaica in relation to ethnic composition, test exercise performance, and habitual physical activity
Authors: G. J. Miller, M. J. Saunders, R. J. C. Gilson, M. T. Ashcroft
Journal: Thorax (1977)

Lung function and physical activity in Jamaican children Guinea the active highland children and less active coastal children, who have been isolated from each other until recent years, are genetically distinct in some respects (Beaven et al., 1972;Harvey, 1974).Ekblom (1969) studied the effects of physical training on boys.Although no ap- parent effect was observed after six months, the results did suggest increased lung growth and development after 32 months' training.The author noted, however, that those who trained for the full period had the larger vital capacity even before the beginning of training.A consideration of the effects of sex, ethnic origin, and physical activity on lung function is important in those parts of the world, such as the Caribbean, where there exist large differences in ethnic background and way of life within populations.The present study was undertaken in Jamaica in order to assess the contributions made by these characteristics to variation in lung func- tion and exercise performance during childhood.
Clinical efficacy and endocrine activity of vorozole in postmenopausal breast cancer patients. Results of a multicentric phase II study
Authors: F. Boccardo, D. Amoroso, S. Iacobelli, L. Irtelli, A. Farris, G. Mustacchi, M. Mesiti, F. Brema, P. Pacini, E. Cortesi, P. Nardini, G. Guida, C. Langenaeken
Journal: Annals of Oncology (1997)
P17.25 * GLIOMA-INITIATING CELL INDUCED INTERLEUKIN-6 PRODUCTION IS MEDIATED BY TOLL-LIKE RECEPTOR 4 IN MICROGLIA
Authors: O. D. a. Dzaye, F. Hu, K. Derkow, P. Euskirchen, C. Harms, S. Lenhardt, S. A. Wolf, H. Kettenmann, M. Synowitz
Journal: Neuro-Oncology (2014)

OBJECTIVE: Malignant gliomas are the most frequent primary tumours of the brain with poor clinical prognosis. Infiltrating peripheral macrophages and resident microglia that constitute the dominant tumour-[[Unsupported Character - Codename ­]]-infiltrating cells in glioblastoma are induced by the glioma cells to become immunosuppressive and tumour supportive. Glioma-[[Unsupported Character - Codename ­]]-initiating cells (GIC) could potentially promote this pro-[[Unsupported Character - Codename ­]]-tumorigenic phenotype. Exploring the interaction between GIC and glioma associated microglia/macrophages (GAM) may offer us an opportunity to further understand the cellular and molecular features of the GIC niche. We here investigate the potential of GIC versus bulk cells to induce a pro-[[Unsupported Character - Codename ­]]- tumorigenic microglial cytokine profile. METHODS: In the present study we stimulated primary cultured microglia with glioma conditioned medium (GCM) from GICs enriched or depleted GL261 cells and cytokine levels were determined by FlowCytomix. RESULTS: An almost 4-[[Unsupported Character - Codename ­]]-fold upregulation in microglial IL-[[Unsupported Character - Codename ­]]-6 secretion was observed using GCM from GICs while the secretion was unchanged with GCM from GICs depleted GL261 cells. Since Toll-[[Unsupported Character - Codename ­]]-like receptors are pattern recognition receptors that are responsible for pro-[[Unsupported Character - Codename ­]]-inflammatory cytokines release, we screened through all the TLRs and identified TLR4 as the main TLR controlling microglial IL-[[Unsupported Character - Codename ­]]-6 secretion. IL-[[Unsupported Character - Codename ­]]-6R and gp130 are highly expressed in GICs but not in microglial cells. The implantation of GL261-[[Unsupported Character - Codename ­]]-EGFP cells into IL-[[Unsupported Character - Codename ­]]-6 -[[Unsupported Character - Codename ­]]-/-[[Unsupported Character - Codename ­]]- mice resulted in significantly smaller tumours as compared to wild-[[Unsupported Character - Codename ­]]- type control mice. IL-[[Unsupported Character - Codename ­]]-6 and IL-[[Unsupported Character - Codename ­]]-6R are also expressed in human gliomas (which contain up to 30% microglia/macrophages) and inversely correlates with patient survival. CONCLUSIONS: Our results show that GICs, but not the bulk glioma cells initiate microglial IL-[[Unsupported Character - Codename ­]]-6 secretion. IL-[[Unsupported Character - Codename ­]]-6 in turn promotes glioma cell growth and invasion.