tbuckley/cabot-search huggingface dataset:
THU0422 Psychometric Properties of the Brief Fatigue Inventory-Short Form in Systemic Lupus Erythematosus
Authors: S. Al Sawah, A.N. Naegeli
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> A 12-week prospective, observational study was conducted to evaluate the psychometric properties of the Brief Fatigue Inventory-Short Form (BFI-SF)<sup>1</sup> and determine its appropriate use for the measurement of fatigue in systemic lupus erythematosus (SLE) clinical trials. <h3>Objectives</h3> The aim of this study was to validate the performance of BFI-SF in a sample of patients with moderate-to-severe SLE. <h3>Methods</h3> Participants ≥18 years, who self-reported a physician diagnosis of SLE (confirmed by medical record review) and active SLE demonstrated by a Systemic Lupus Activity Questionnaire (SLAQ) score of ≥11 (0-44 scale), were recruited using a free electronic medication monitoring service. All participants completed the BFI-SF, Multidimensional Assessment of Fatigue (MAF), and Medical Outcome Study 36-Item Short Form Health Survey (SF-36) electronically at baseline, week 2, and week 12. Score distributions, internal consistency, test-retest reliability, and construct validity were evaluated. <h3>Results</h3> A total of 122 participants were included in the study. The mean age was 45.7 years, 95.9% were female, and 68.9% were non-Hispanic white. Cronbach9s alpha were &gt;0.9 for all BFI-SF items. Test-retest reliability of the BFI-SF showed a stable intraclass correlation for item #7 (ICC 0.76), and BFI domain scores had higher correlations (around 0.5) than most items (around 0.3-0.4). Construct validity was measured by strength of the correlations of the BFI-SF severity domains and global scores, and were moderately positively correlated to the SLAQ score (r&gt;0.4). The domain and global scores were moderately negatively correlated to the SF-36 Vitality and Physical Function domains and SF-36 Physical Component scores (all r&lt;-0.3). The BFI-SF item #3 for worst fatigue was highly positively correlated to the MAF (r=0.6). Patients with less severe fatigue (MAF≤36) scored lower than patients with more severe fatigue (MAF&gt;36) on all domains of the BFI-SF (total score, 4.66±1.55 vs. 6.80±1.13; p&lt;0.0001). <h3>Conclusions</h3> Assessment of fatigue severity and the impact of fatigue on daily functioning as measured by the BFI-SF demonstrated validity and reliability in a sample of patients with SLE and may be used as a patient-reported outcome tool in clinical trials. <h3>References</h3> Mendoza TR, et al. Cancer 1999;85:1186-96 <h3>Acknowledgements</h3> This research was funded by Eli Lilly and Company, Indianapolis, IN. <h3>Disclosure of Interest</h3> : S. Al Sawah Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, A. Naegeli Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2055
Obstetrician issues writ after embryo mix-up
Authors: C. Dyer
Journal: BMJ (2003)

A consultant obstetrician who headed an in vitro fertilisation unit that was closed after two women were implanted with the wrong embryos is suing her employers for libel over allegations that she mismanaged it.

Lawyers for Geeta Nargund, who was suspended by St George's Healthcare NHS Trust, London, in October, served her libel claim on the trust's lawyers just before Christmas.

She was suspended after it emerged that a mix-up involving the embryos of three women had occurred last April at the Diana, Princess of Wales Centre for Reproductive Medicine at St George's Hospital Medical School. The embryos …
Leprosy in reaction: a medical emergency.
Authors: A S Malin, M F Waters, S A Shehade, M M Roberts
Journal: BMJ (1991)

better patient care and savings.'7This aspect should be addressed firstly on the basis of asking the question "Is the therapeutic ratio favourable and realistically con- structed for this patient and this proposed treatment?"and not "Is it more cost effective to treat this patient than another patient?"I Senile dementia of Alzheimer's type-normal ageing or disease?[Editorial.]
Subversion of the innate immune response by micro-organisms
Authors: B Fernie-King, D J Seilly, A Davies, P J Lachmann
Journal: Annals of the Rheumatic Diseases (2002)

A microbe becomes a pathogen by successfully evading the host’s immune responses, and the microbial strategies for so doing are legion. They include methods to avoid recognition by the immune system—for example, by antigenic variation as shown by influenza and HIV and by parasites or plasmodia, or by acquiring a host coat as is done by worms and retroviruses.

Another major mechanism is to avoid the effector mechanisms of the immune response. This can be done by subverting cytotoxic T cells by the production of decoy HLA molecules; or by subverting Fc function by producing Fc receptor homologues; or by subverting complement by producing homologues of complement control proteins (CCPs). Some viruses also have developed methods of subverting apoptosis in the cells that they infect.

This paper concentrates on the innate immune response. The definition of this term is a little fuzzy. Fearon and Locksley regard all mechanisms using germline coded molecules as being innate which therefore includes natural antibodies with germline V regions.1 Perhaps a more conventional definition is that innate mechanisms are those that are not specifically altered by prior exposure to the same pathogen.

In the first part of this paper some examples of subversion of the complement system will be described. The second half describes some much newer work from our laboratory that takes us into aspects of the innate immune response on mucosal surfaces that have not so far been described.

Figure 1 shows a greatly simplified view of complement activation by micro-organisms. Regulation occurs principally at two points—the first is action of the C3 converting enzymes and the second, action of the membrane attack complex (MAC).



 Figure 1  
Principal activities of the complement system.



Regulation of the C3 converting enzymes is produced by a number of proteins (fig 2), all of which are based on …
Gap junctions in preconditioning against arrhythmias
Authors: E LASCANO, J NEGRONI
Journal: Cardiovascular Research (2007)

See article by Papp et al .  [10]  (pages 396–405) in this issue . 

Ischemic preconditioning is a natural mechanism by which brief periods of ischemia–reperfusion initiate a complex cascade of events that culminate in the protection of the heart against a subsequent sustained ischemia, reducing infarct size, postischemic dysfunction, and the incidence of arrhythmias [1]. In essence, endogenous or exogenous triggers released during ischemic or pharmacological preconditioning activate mediators that act on end-effectors, preserving mitochondrial, cytoskeletal, and cell membrane integrity [2]. However, although much effort has been dedicated to the study of preconditioning mechanisms, these have not been clearly elucidated, and in particular the pathways involved in the protection against arrhythmias have not been as thoroughly investigated as those concerning infarct size.

One of the proposed targets of preconditioning protection is gap junctions. These intercellular structures formed by two hemichannels of connexin-43 (Cx43) mediate the exchange of small molecules and ions between two adjacent cells and play an active role in the electrical synchronization of the heart. Phosphorylation of Cx43 regulates gap junction conductance and permeability. In the normoperfused heart, most Cx43 is phosphorylated, allowing cell-to-cell coupling and the propagation of depolarization in the myocardial syncytium. During the course of ischemia, however, … 

*Corresponding author. Tel.: +54 11 4378 1187; fax: +54 11 4381 0323. Email address: lascano{at}favaloro.edu.ar
Abstract B4: A microRNA screen to identify modulators of sensitivity to Bcl-2 inhibitor ABT-263
Authors: Dimitri Semizarov, Lloyd Lam, Xin Lu
Journal: Clinical Cancer Research (2010)

Abstract Evasion of apoptosis is a known feature of cancer cells. One mechanism of deregulating the apoptotic pathway is through overexpression of anti-apoptotic Bcl-2 family members. ABT-263 is a first-in-class Bcl-2 family inhibitor that restores the ability of cancer cells to undergo apoptosis. However, many cancer cells are resistant to ABT-263 due to high levels of a Bcl-2 family member Mcl-1, which is not targeted by the drug. Mcl-1 expression is known to be regulated transcriptionally, translationally, and through proteosome-mediated degradation. Recently, Mcl-1 expression was shown to be affected by microRNAs (miRNAs). In order to identify miRNAs that modulate the sensitivity of cancer cells to ABT-263, we screened a library of 810 human miRNA mimics in HCT-116 cells in the presence of ABT-263. The screen revealed 19 miRNAs that sensitize HCT-116 cells to ABT-263. Fifteen of these miRNAs were also shown to sensitize CHL1 melanoma cells to the same agent. We further evaluated twelve of the strongest sensitizers in these cell lines. We found that these sensitizers induced apoptosis only in the presence of ABT-263. In addition, while all twelve of these miRNAs reduced Mcl-1 protein expression, only ten of them targeted Mcl-1 through direct binding to the Mcl-1 3′ untranslated regions (3′-UTR) of the gene. Other resistance pathways and regulators of Mcl-1 expression may be identified using this method. Our data can be used to design miRNA replacement therapies to increase sensitivity to Bcl-2 antagonists. The expression of the 12 marker microRNAs is now being correlated to the sensitivity to ABT-263 in order to enable rational patient selection in ABT-263 clinical trials. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B4
Induction of Apoptosis of Metastatic Mammary Carcinoma Cells In Vivo by Disruption of Tumor Cell Surface CD44 Function
Authors: Qin Yu, Bryan P. Toole, Ivan Stamenkovic
Journal: The Journal of Experimental Medicine (1997)

To understand how the hyaluronan receptor CD44 regulates tumor metastasis, the murine mammary carcinoma TA3/St, which constitutively expresses cell surface CD44, was transfected with cDNAs encoding soluble isoforms of CD44 and the transfectants (TA3sCD44) were compared with parental cells (transfected with expression vector only) for growth in vivo and in vitro. Local release of soluble CD44 by the transfectants inhibited the ability of endogenous cell surface CD44 to bind and internalize hyaluronan and to mediate TA3 cell invasion of hyaluronan-producing cell monolayers. Mice intravenously injected with parental TA3/St cells developed massive pulmonary metastases within 21–28 d, whereas animals injected with TA3sCD44 cells developed few or no tumors. Tracing of labeled parental and transfectant tumor cells revealed that both cell types initially adhered to pulmonary endothelium and penetrated the interstitial stroma. However, although parental cells were dividing and forming clusters within lung tissue 48 h following injection, &amp;gt;80% of TA3sCD44 cells underwent apoptosis. Although sCD44 transfectants displayed a marked reduction in their ability to internalize and degrade hyaluronan, they elicited abundant local hyaluronan production within invaded lung tissue, comparable to that induced by parental cells. These observations provide direct evidence that cell surface CD44 function promotes tumor cell survival in invaded tissue and that its suppression can induce apoptosis of the invading tumor cells, possibly as a result of impairing their ability to penetrate the host tissue hyaluronan barrier.
Abstract 51: Elevated levels of <i>E2F1</i>, <i>EZH2</i> and <i>SUZ12</i> lead to invasive progression of superficial bladder cancers
Authors: Se-Ra Lee, Yun-Gil Roh, Won-Tae Kim, Seon-Kyu Kim, Jeonghoon Heo, In-Sun Chu, Sun-Hee Leem
Journal: Cancer Research (2014)

Abstract Bladder cancer is increasing a rate of occurrence in aging societies. A superficial bladder cancer is noninvasive that is presented as a good prognosis after receiving treatment. However, about 20∼50% of superficial bladder cancer patients progressed to invasive tumor which represent the poor survival rates within 5 years. In previous study, we addressed if the transcriptional characteristics of the superficial bladder cancer could be used as predictive biomarkers for the progression of superficial tumors to invasive ones. Using gene expression data from 165 bladder cancer patients, we identified a gene expression signature that could predict the likelihood of progression to invasive tumors. Gene network analyses of the signature revealed that E2F1 and its downstream effectors EZH2 and SUZ12 could be important mediators for the invasive and metastatic progression of superficial tumors. In this study, we investigated how these genes may affect the invasive and metastatic progression of superficial tumors. For confirmation of the expression of E2F1, EZH2 and SUZ12 in two groups of bladder cancer cells, we performed quantitative RT-PCR and western blot assay. Both of mRNA and protein expression of E2F1, EZH2 and SUZ12 in superficial bladder cancer were significantly lower than invasive bladder cancer cells (p&amp;lt; 0.0001). Next, we performed an invasion and migration assay. The overexpression of E2F1, EZH2 and SUZ12 presented an increase of invasiveness and migratory in UC9 superficial bladder cancer. On the other hand, the silencing of gene expression in EJ invasive cell was shown a significantly decreasing of invasiveness and migratory ability. Also, we determine the effect of proliferation and colony formation in superficial and invasive bladder cancer. The depletion of E2F1, EZH2 and SUZ12 in EJ and 5637 invasive bladder cancer cells that significantly decreasing of forming colonies on soft agar. Furthermore, we founded the reduction of tumor size when injected cells depleted E2F1, EZH2 and SUZ12 than control by xenograft assay. Together, our findings reveal that the estimating the roles of E2F1, EZH2 and SUZ12 for the invasive and metastatic progression in superficial bladder cancer. Citation Format: Se-Ra Lee, Yun-Gil Roh, Won-Tae Kim, Seon-Kyu Kim, Jeonghoon Heo, In-Sun Chu, Sun-Hee Leem. Elevated levels of E2F1, EZH2 and SUZ12 lead to invasive progression of superficial bladder cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 51. doi:10.1158/1538-7445.AM2014-51
Increased IgG4 responses to multiple food and animal antigens indicate a polyclonal expansion and differentiation of pre-existing B cells in IgG4-related disease
Authors: Emma L Culver, Ellen Vermeulen, Mateusz Makuch, Astrid van Leeuwen, Ross Sadler, Tamsin Cargill, Paul Klenerman, Rob C Aalberse, S Marieke van Ham, Eleanor Barnes, Theo Rispens
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition, characterised by an elevated serum IgG4 concentration and abundant IgG4-positive plasma cells in the involved organs. An important question is whether the elevated IgG4 response is causal or a reflection of immune-regulatory mechanisms of the disease. <h3>Objectives</h3> To investigate if the IgG4 response in IgG4-RD represents a generalised polyclonal amplification by examining the response to common environmental antigens. <h3>Methods</h3> Serum from 24 patients with IgG4-RD (14 treatment-naive, 10 treatment-experienced), 9 patients with primary sclerosing cholangitis and an elevated serum IgG4 (PSC-high IgG4), and 18 healthy controls were tested against egg white and yolk, milk, banana, cat, peanut, rice and wheat antigens by radioimmunoassay. <h3>Results</h3> We demonstrated an elevated polyclonal IgG4 response to multiple antigens in patients with IgG4-RD and in PSC-high IgG4, compared with healthy controls. There was a strong correlation between serum IgG4 and antigen-specific responses. Responses to antigens were higher in treatment-naive compared with treatment-experienced patients with IgG4-RD. Serum electrophoresis and immunofixation demonstrated polyclonality. <h3>Conclusions</h3> This is the first study to show enhanced levels of polyclonal IgG4 to multiple antigens in IgG4-RD. This supports that elevated IgG4 levels reflect an aberrant immunological regulation of the overall IgG4 response, but does not exclude that causality of disease could be antigen-driven.
Israeli medical humanitarian group is to share alternative Nobel prize
Authors: J. Siegel-Itzkovich
Journal: BMJ (2010)

<h3>Objective:</h3> Effect of Botox lasts more than 120 days in neuromuscular junction and in some cases up to nine months, using single fiber EMG technique. <h3>Background:</h3> Botox injection has been used for different purposes including cosmetic and treatment of migraine headache. Based on available data Botox effects last 120 days after injection. We have had several cases of ptosis who were referred to us around 3–4 months after Botox injection to rule out ocular myasthenia. <h3>Design/Methods:</h3> We performed single fiber EMG on 2 cases of ptosis and 2 asymptomatic volunteer, all with history of Botox injection 3 months prior to referral to us. Follow up single fiber was performed 6, 9 and 12 months after injection. We sampled at least 10 pairs from frontalis muscle of each subject. <h3>Results:</h3> Single fiber EMG was significantly abnormal in all cases 3 months after Botox injection with more than 50 % of pairs abnormal with increased jitter and blocks. Follow up Single fiber 6 months after injection showed a drop in abnormal pairs to 30% and by 9 months 1 out of 10 pairs was abnormal. In most cases single fiber became completely normal one year after injection. <h3>Conclusions:</h3> Effect of Botox last up to 9 months after injection using single fiber EMG. In case of a subject with ptosis and history of Botox injection, we recommend a baseline single fiber EMG and then follow ups 6, 9 and 12 months after injection. These data would decrease the number of false positive ocular mysthenia. <b>Study Supported by:</b> NA <b>Disclosure:</b> Dr. Bayat has nothing to disclose. Dr. Russo has nothing to disclose.
Towards explaining health inequalities
Authors: M. Bartley
Journal: BMJ (2000)

EDITOR—Vagero's editorial has opened up an issue that our paper on health inequality in men and women did not discuss in any detail.1 2 Research into health inequality now aims to move away from description and towards explanation. This means that measures of socioeconomic position need to be chosen with reference to hypotheses about how health inequalities are produced. In …
Auscultatory Findings in Patients with Cardiac Pacemakers
Authors: KABI P. MISRA
Journal: Annals of Internal Medicine (1971)

The use of pacemakers has resulted in a variety of interesting auscultatory findings. The nature of these findings depends on the mode of pacing, the atrial rhythm, the integrity of atrioventricular and ventriculoatrial conduction, and abnormal sounds or murmurs presumably produced by malposition of the pacemakers. These auscultatory findings are reviewed with illustrations. An understanding of these phenomena is useful for proper clinical evaluation of the pacer function.
Treatment of Hypercholesterolemia with Nicotinic Acid
Authors: RICHARD W. P. ACHOR, KENNETH G. BERGE, NELSON W. BARKER, BERNARD F. MCKENZIE
Journal: Circulation (1958)

Nicotinic acid was administered orally to 33 patients with hypercholesterolemia in doses varying from 1.5 to 6.0 Gm. per day for periods of 3 months to 1½ years. Significant, sustained, and reproducible decreases in the concentration of cholesterol and total lipids in the plasma and of serum beta-lipoprotein cholesterol were observed in a majority of patients. This form of therapy appears to be effective, practical, and probably free from serious harmful effects.
Reply
Authors: Jean‐Charles Nault, Julien Calderaro, Jessica Zucman‐Rossi
Journal: Hepatology (2015)

We thank Ko et al. for their comments about our article1 and their description of telomerase reverse transcriptase (TERT) promoter hypermethylation as a potential mechanism of TERT reactivation and a prognostic biomarker in a series of hepatocellular carcinoma (HCC) from Korea. Telomere shortening and absence of telomerase activity are involved in cirrhosis pathogenesis, but telomerase reactivation is required in tumor initiation and progression. Overall, more than 90% of HCC harbored an increased TERT expression. We described somatic TERT promoter mutations in 60% of human HCCs leading to increased TERT expression.2 However, other genetic and viral mechanisms can cause TERT reexpression. Insertional mutagenesis of hepatitis B virus (HBV) in the TERT promoter has been described in approximately 15%-20% of HBV-related HCC.3 In addition, TERT amplification was recently identified in 5%-6% of HCC and was associated with an increase TERT expression.4, 5 Interestingly, each of these mechanisms (TERT promoter mutation, TERT amplification, and HBV insertion in the TERT promoter) seems to be exclusive together in a large number of HCCs. However, 20%-30% of HCCs show TERT overexpression without underlying genetic or viral explanations. As underlined by Ko et al., epigenetic modification resulting from hypermethylation of the TERT promoter could be one of the mechanism leading to TERT overexpression. However, future studies are warranted to search for TERT promoter hypermethylation in cohorts of Western patients with HCC and determine whether this potential epigenetic mechanism is exclusive from other genetic and viral mechanism known to increase TERT messenger RNA. Jean-Charles Nault, M.D.1,2,3,4,5 Julien Calderaro, M.D., Ph.D.1,2,3,4,6 Jessica Zucman-Rossi, M.D., Ph.D.1,2,3,4,7 1Inserm UMR-1162 Génomique fonctionnelle des Tumeurs solides Equipe Labellisée Ligue Contre le Cancer Paris, France 2Université Paris Descartes Labex Immuno-Oncology Sorbonne Paris Cité Faculté de Médecine Paris, France 3Université Paris 13 Sorbonne Paris Cité UFR SMBH Bobigny, France 4Université Paris Diderot Paris, France 5Assistance Publique–Hôpitaux de Paris Hôpitaux Universitaires Paris–Seine Saint-Denis Site Jean Verdier Pôle d'Activité Cancérologique Spécialisée Service d'Hépatologie Bondy, France; 6Assistance Publique–Hôpitaux de Paris Department of Pathology CHU Henri Mondor Créteil, France 7Assistance Publique–Hôpitaux de Paris Hopital Europeen Georges Pompidou Paris, France Author names in bold designate shared co-first authorship.
Applying the Evidence in Australia
Authors: Norman Swan
Journal: JAMA (1999)

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