tbuckley/cabot-search huggingface dataset:
Pseudomonas aeruginosa causes endoplasmic reticulum (ER) stress in bronchial epithelial cells via its virulence factors pyocyanin (PCN) and alkaline protease (AP)
Authors: Emily F.A. van 't Wout, Annemarie van Schadewijk, Ria A.M. Tommassen-van Boxtel, Jan Stolk, Jan P.M. Tommassen, Stefan J. Marciniak, Pieter S. Hiemstra
Journal: European Respiratory Journal (2013)

P. aeruginosa  infection significantly increases morbidity and mortality of cystic fibrosis and COPD. This has been ascribed to a variety of virulence factors, including secreted PCN and AP. Efficient ER functioning is crucial for cellular homeostasis, while an excess of unfolded proteins leads to “ER stress” and activation of the “unfolded protein response” (UPR). Bacterial infection and TLR activation trigger the UPR, most likely through increased biosynthesis of secreted inflammatory mediators. We hypothesized that PCN and AP secreted by  P. aeruginosa  increase UPR signaling in bronchial epithelial cells.  Conditioned medium from cultures of  P. aeruginosa  strain PAO1 activated the UPR, as evidenced by an increase of splicing of  XBP1  mRNA (12-fold; p CHOP  mRNA (13-fold; p=0.02) and  GADD34  mRNA (16-fold; p GADD34  mRNA. In addition, purified PCN also increased splicing of  XBP1  mRNA and the expression of  CHOP  and  GADD34  mRNA (all p XBP1  mRNA and less up-regulation of  CHOP  mRNA compared to the wild-type strain.  In summary,  P. aeruginosa  virulence factors activate the UPR, and specifically PCN and AP contribute to this phenomenon through different pathways.  This study was supported by grant 3.2.08.032 from the Netherlands Asthma Foundation.
Testing hypotheses: reply
Authors: Michael S Kramer
Journal: BMJ (2007)

<h3>Objective</h3> Prediction of post-operative residual disease after ovarian cancer cytoreductive surgery remains a topic of interest to gynecologic oncologists. The aim of this study was to explore the correlation between serum CA125, peritoneal cancer index, and intra-operative mapping of ovarian cancer and their predictive value for post-operative outcome. <h3>Methods</h3> A total of 70 patients with primary epithelial ovarian cancer, who underwent primary cytoreductive surgery at Charité, Berlin between January 2013 and February 2014 were included. In all patients, pre-operative CA125 values, intra-operative peritoneal cancer index, and intra-operative mapping of ovarian cancer were determined. <h3>Results</h3> Using a receiver operating characteristic analysis, cut-off values for CA125, peritoneal cancer index, and intra-operative mapping of ovarian cancer score could be defined. Patients with pre-operative serum CA125 &gt;600 U/mL had a three times higher risk for residual tumor after primary cytoreductive surgery (p=0.037). A peritoneal cancer index score &gt;20 indicated a nine times increased risk for residual tumor (p=0.003). More than six affected abdominopelvic fields on the intra-operative mapping of ovarian cancer was associated with a 25 times higher risk of residual tumor after primary cytoreductive surgery (p≤0.05). The combination of all three values predicted residual tumor in up to 90% of patients. <h3>Conclusion</h3> We found that pre-operative CA125 &gt;600 U/mL, peritoneal cancer index &gt;20, and intra-operative mapping of ovarian cancer score &gt;6 could be used as predictors of complete tumor resection. The combination of all these three values predicted the incomplete resection of disease in up to 90% of patients even in experienced centers.
Abstract 3499: Improving therapeutic efficacy of Docetaxel in breast cancer
Authors: Jeronay King, Hina Mir, Neeraj Kapur, Shailesh Singh
Journal: Cancer Research (2015)

Abstract Chemotherapy is the preferred choice for treatment of advance breast cancer (BrCa). In most cases, cytotoxic drugs are used at or near a maximum tolerated dose (MTD) to achieve maximum response and eradicate the neoplastic cells, at the same time MTD doses are often toxic and have severe side effects. Lower dose i.e. “optimal biological response modifier dose” (OBRMD) provides potentially beneficial responses, but is not capable of achieving optimal clinical response. Hence, the focus of this study was to achieve the optimal therapeutic outcome of Docetaxel (DTX) at a lower dose by using it in combination with Apigenin (API), a dietary flavonoid present in fruits and vegetables. Effect of DTX and API, either alone or in combination on BrCa cells viability and apoptosis was determined by MTT assay and flow cytometry, respectively. We further investigated the mechanism of enhanced efficacy of DTX using western blot analysis and real time qPCR. Significant decrease in cell viability was observed when cells were treated with low dose DTX in combination with API as compared to either of the agent used individually in MDA-MB-231, MDA-MB-468 and MCF 10A cells. Real time analysis showed that API up regulates pro-apoptotic molecules and down regulates anti-apoptotic molecules when using in combination with DTX. These findings suggest that Apigenin is capable of reducing the effective dose of docetaxel. Hence, this new modality may have better therapeutic outcome with minimal or no toxicity. Citation Format: Jeronay King, Hina Mir, Neeraj Kapur, Shailesh Singh. Improving therapeutic efficacy of Docetaxel in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3499. doi:10.1158/1538-7445.AM2015-3499
Prognostic Impact of Hypertrabeculation and Noncompaction Phenotype in Dilated Cardiomyopathy
Authors: Mihaela-Silvia Amzulescu, Michel F Rousseau, Sylvie A Ahn, Laurianne Boileau, Christophe de Meester de Ravenstein, David Vancraeynest, Agnes Pasquet, Jean Louis Vanoverschelde, Anne-Catherine Pouleur, Bernhard L Gerber
Journal: JACC. Cardiovascular imaging (2015)
Restrictive mitral annuloplasty with or without surgical ventricular reconstruction in ischaemic cardiomyopathy: impacts on neurohormonal activation, reverse left ventricular remodelling and survival
Authors: Satoshi Kainuma, Kazuhiro Taniguchi, Koichi Toda, Toshihiro Funatsu, Shigeru Miyagawa, Haruhiko Kondoh, Takafumi Masai, Shigeaki Otake, Yasushi Yoshikawa, Hiroyuki Nishi, Taichi Sakaguchi, Takayoshi Ueno, Toru Kuratani, Takashi Daimon, Yoshiki Sawa
Journal: European Journal of Heart Failure (2013)
Gastrointestinal Polyposis and Nonpolyposis Syndromes
Authors: Coyle T
Journal: New England Journal of Medicine (1995)

We believe that the description of Turcot's syndrome by Rustgi maintains the confusion that has existed in the literature since the original description of the association between polyposis and central nervous system tumors. We think that there are two distinct conditions: autosomal dominant familial adenomatous polyposis with central nervous system tumors as extracolonic features and autosomal recessive Turcot's syndrome with central nervous system tumors as primary features.
Laparoskopik Nefroüreterektomiye Karşı Açık Nefroüreterektomi: Randomize Prospektif Bir Çalışmaya Ait Perioperatif ve Onkolojik Sonuçlar
Authors: Giuseppe Simone, Rocco Papalia, Salvatore Guaglianone, Mariaconsiglia Ferriero, Costantino Leonardo, Ester Forastiere, Michele Gallucci
Journal: European Urology (2009)
Origins of DSM-I: a study in appearance and reality
Authors: G N Grob
Journal: American Journal of Psychiatry (1991)

The author traces the history of psychiatric nosology in the United States from its origins in the early nineteenth century to the introduction of DSM-I in 1952. Until World War I, psychiatrists were not interested in systematic classification, although they were concerned with diagnosis. The first official nosology, adopted in 1918, reflected the need to collect mental hospital data. The federal Bureau of the Census had a role in the development of this nosology in that it required such data. The publication of DSM-I marked an internal transformation that mirrored the growing dominance of psychodynamic and psychoanalytic psychiatry and the relative weakness of the biological tradition. This transformation occurred largely as a result of the lessons learned by psychiatrists during World War II. The author's basic argument is that nosology reflected not only psychiatric ideology but also other, external determinants at any given point in time.
Abstract 15570: A Novel Ex Vivo Test System to Assess Cardiovascular Toxicity of HIV-Nef in PBMC From HIV Positive Donors
Authors: Matthias Clauss, Linden A Green, Tina Wang, Sarvesh Chelvanambi, Samir K Gupta
Journal: Circulation (2014)

Background: To address how cardiovascular disease is increased in HIV patients with and without therapy, we have tested the effects of HIV-infected T cell when in contact to human coronary endothelial cells (HCAEC). We found that these T cells could induce endothelial dysfunction and cell death at a much larger extent than free virus itself. We could identify HIV-Nef protein, a major pathogenic factor in HIV disease progression and HIV-induced end organ disease, as the mechanism for this finding. Because of our finding that HIV-Nef is transferred from T cells to HCAEC to induce cell death, we asked whether PBMC form HIV-infected patients can recapitulate these findings. Methods: PBMC were isolated from either healthy donors or from untreated HIV patients or from those on ART using standard Ficoll purification, and intracellular Nef was determined by flow cytometry and ELISA. PBMC were co-cultivated with HCAEC for 24 hours, washed off and HCAEC were analyzed for Nef by immunofluorescence microscopy representation and ELISA. Further, HCAEC were analyzed for apoptosis by TUNEL. Results: HIV-Nef protein was found in PBMC of untreated HIV-positive and surprisingly also in patients receiving virally suppressive anti-retroviral therapy (ART). Importantly, we could demonstrate in untreated HIV patients Nef protein transfer to HCAEC and increased induction of endothelial apoptosis (see figure, ** p&lt;0.01). Currently, equivalent studies with PBMC from patients on ART are in progress. Conclusion: This study demonstrates that Nef-positive PBMC at least in untreated HIV patients can be transferred to HCAEC to cause endothelial cell apoptosis. This will be the basis for future studies analyzing the role of NADPH oxidases and reactive oxygen species in this toxic activity of Nef. Based on this assay system we can address the hypothesis that HIV-Nef plays a pivotal role in the development of cardiovascular diseases in HIV patients with or without ART.
Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial
Authors: Jeremy Sokolove, Michael Schiff, Roy Fleischmann, Michael E Weinblatt, Sean E Connolly, Alyssa Johnsen, Jin Zhu, Michael A Maldonado, Salil Patel, William H Robinson
Journal: Annals of the Rheumatic Diseases (2015)

Objectives To examine whether baseline anti-cyclic citrullinated peptide-2 (CCP2) antibody status and concentration correlated with clinical outcomes in patients treated with abatacept or adalimumab on background methotrexate (MTX) in the 2-year AMPLE (Abatacept versus adaliMumab comParison in bioLogic-naïvE rheumatoid arthritis subjects with background MTX) study. Methods In this exploratory analysis, anti-CCP2 antibody concentration was measured at baseline, and antibody-positive patients were divided into equal quartiles, Q1–Q4, representing increasing antibody concentrations. Clinical outcomes analysed by baseline anti-CCP2 status and quartile included change from baseline in disease activity and disability and remission rates. Results Baseline characteristics were generally comparable across quartiles and treatment groups. In both treatment groups, anti-CCP2 antibody-negative patients responded less well than antibody-positive patients. At year 2, improvements in disease activity and disability and remission rates were similar across Q1–Q3, but were numerically higher in Q4 in the abatacept group; in contrast, treatment effects were similar across all quartiles in the adalimumab group. Conclusions In AMPLE, baseline anti-CCP2 positivity was associated with a better response for abatacept and adalimumab. Patients with the highest baseline anti-CCP2 antibody concentrations had better clinical response with abatacept than patients with lower concentrations, an association that was not observed with adalimumab. Trial registration number NCT00929864.
STUDIES IN CONGESTIVE HEART FAILURE
Authors: J. Alfed Calhoun, Glenn E. Cullen, Gurney Clarke, T. R. Harrison
Journal: Journal of Clinical Investigation (1930)

In one of the previous studies of this series it was shown that the cardiac and skeletal muscles of patients dying of congestive heart failure were abnormally poor in potassium, Harrison, PMlcher and Ewing (1930).The loss of-potassium from skeletal muscle appeared to be related to edema, as muscles which were not edematous con- tained normal amounts of potassium.Pieces of skeletal muscles removed during life contained less potassium when the patients were edematous than when they were edema free.It appears therefore that the presence of edema is an important cause of the loss of potas- sium in skeletal muscle.The present study was undertaken in an attempt to determine the cause of the loss of potassium from the cardiac muscle. METHODTissues were obtained at the postmortem table.Pieces of ventric- ular muscle weighing 5 to 20 grams were freed of fat, weighed and dried to constant weight at 105 to 110°C.One to two decigrams of the dried muscle were digested with nitric acid as described by Van Slyke (1924) for chloride determinations.The nitric acid was then driven off by evaporation, and the residue was freed of ammonia by boiling with excess sodium hydroxide.The mixture was then neutral- ized with sulphuric acid.Potassium was precipitated as the cobalti-
Brain disease and psychiatric illness: when should a psychiatrist order a CAT scan?
Authors: Weinberger Dr
Journal: American Journal of Psychiatry (1984)

Because psychiatric symptoms are frequently the earliest signs of CNS pathology, the author outlines the structural brain diseases that may underlie several psychiatric syndromes and describes the computerized axial tomographic (CAT) scan findings associated with those diseases. On the basis of an awareness of these conditions and a cost-benefit analysis, the following indications for CAT scanning of psychiatric patients are proposed: 1) confusion and/or dementia of unknown cause, 2) first episode of a psychosis of unknown etiology, 3) movement disorder of unknown etiology, 4) anorexia nervosa, 5) prolonged catatonia, and 6) first episode of major affective disorder or personality change after age 50.
An international perspective on assessment of negative and positive symptoms in schizophrenia
Authors: Massimo Moscarelli, Cesare Maffei, Bruno M. Cesana, Paolo Boato, Tommaso Farma, Adele Grilli, Vittorio Lingiardi, Carlo Lorenzo Cazzullo
Journal: American Journal of Psychiatry (1987)

The authors used the Scale for Assessment of Negative Symptoms and the Scale for Assessment of Positive Symptoms in interviews of 96 psychiatric inpatients in Italy. They evaluated the interrater reliability and the internal consistency of these scales for the assessment of negative and positive symptoms in schizophrenia. Their findings indicate that the results of these scales are similar in Italy and the United States, countries with different languages and cultures.
Abstract 17005: Effects of Evolocumab Treatment on Serum Adrenal and Gonadal Hormone Levels: Results from the 52-week, Phase 3, Double-blind, Randomized, Placebo-controlled DESCARTES Study
Authors: Dirk J Blom, C. Stephen Djedjos, Kate Tsirtsonis, Scott M Wasserman, Rob Scott, Eli Roth
Journal: Circulation (2014)

Introduction: Evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), markedly reduces LDL-C in clinical studies. We evaluated adrenal and gonadal steroid hormone metabolism in evolocumab-treated patients, as LDL uptake may be an important source of cholesterol for steroid hormone synthesis. Methods: DESCARTES (NCT01516879) randomized patients receiving lipid-lowering therapy to 52 weeks of subcutaneous monthly evolocumab 420 mg or placebo in a 2:1 ratio. We measured adrenal (cortisol and corticotropin [ACTH]) and gonadal hormones (estradiol and follicle stimulating hormone [FSH]) in females; testosterone and luteinizing hormone [LH] males) at baseline and at week 52. Results were stratified by minimum post-baseline LDL-C. We excluded patients receiving hormone replacement therapy, those with elevated baseline gonadotropins, and females older than 50 years from gonadal hormone analyses. Results: There was no decrease in steroid or increase in pituitary stimu...
Clinical significance of autoantibody screening in patients with idiopathic pulmonary fibrosis
Authors: Morven E.M. Wilkie, James D. Chalmers, Robin P. Smith, Stuart Schembri
Journal: European Respiratory Journal (2013)

Introduction

Autoantibody screening is frequently performed in patients with idiopathic pulmonary fibrosis (IPF), but the clinical relevance of positive autoantibodies without clinically objective connective tissue disease is unclear.

Methods

A retrospective analysis was made of 114 patients with IPF. Data was collected on all autoimmune tests performed. Patients were followed up for 3 years or until death.

Results

Median age was 72 years (interquartile range 65-77). 61.4% male. 42 had positive autoantibody testing (36.8%). Antinuclear antibody (ANA) was positive in 28.9%. 11 patients had positive antineutrophil cytoplasmic antibody (ANCA). 6 patients had positive rheumatoid factor and 1 had positive cyclic citrullinated peptide test.

Comparing patients with positive tests and those without, positive autoantibodies were more frequently seen in females (64.8% vs 31.1%,p=0.01). Patients with positive autoantibodies were of similar age (median age 73 years IQR 67-77 vs median 69 years 62-78,p=0.3).

Using the GAP index, a validated prognostic tool in IPF, the severity of lung disease was greater in the autoantibody positive group-mean score 3.7 SD 1.4 in the positives and 3.1 SD 1.5 in the negatives, p=0.048.

Mortality rate was 31% in the autoantibody positive group and 13.9% in the negative group. Adjusting for baseline difference in severity between the groups, positivity was not associated with increased mortality (adjusted odds ratio 1.63 95% CI 0.53-5.03,p=0.4).

Conclusion 

In our cohort, positive autoantibodies are common in IPF and are more common in female patients with more severe disease. However, positive autoantibodies do not appear to be an independent predictor of poor outcome.
Fertility and Sex Ratio of Offspring of Female HBsAg Carriers
Authors: D Livadas, J Economidou, J E Hesser, D A Koutras, S Hadziyannis
Journal: Journal of the Royal Society of Medicine (1979)

The relation of the HBsAg carrier state with fertility parameters and the sex ratio of offspring was studied in 1129 married women in 12 villages from different areas in Greece, in whom blood samples were tested for HBsAg. The results were compared between the group of HBsAg asymptomatic carriers and the HBsAg-negative group. An increase of the sex ratio was found in the group of HBsAg carriers. Furthermore, a decrease in the live births and a reduction in the number of female children were observed. It is concluded that a fertility disturbance in the HBsAg-positive group is probably responsible for the alteration of the sex ratio. An immunological mechanism may be the cause of the fertility disturbance found in the HBsAg carriers.
Aspirin prophylaxis for vascular disease
Authors: D Fitzmaurice, C P Thomas, H. Chant, S. Fearn, C. McCollum, M. Eccles, N. Freemantle, J. Mason
Journal: BMJ (1998)

Editor—We read with interest the recent articles from the North of England evidence based guideline development project.1,2 We represent the Birmingham Clinical Effectiveness Group and admire the rigour with which these guidelines have been developed. The effort required to synthesise this amount of evidence cannot be underestimated, but has the effort been worth while?

None of the guidelines provides new evidence, and, given the basic requirement for evidence based medicine to answer a clinically relevant question, their value is questionable. For example, it is well known that aspirin after myocardial infarction is beneficial.3 The challenge lies in increasing the use of aspirin in this clinical situation, in changing behaviour rather than simply improving knowledge. We wonder whether these guidelines will effect change such that aspirin use is increased. Similarly, it has been recognised for some time that the use of angiotensin converting enzyme inhibitors is beneficial for patients with cardiac failure, and the challenge remains the same.

Maybe the effort and funding expended in reinforcing what is already known might have been better directed in trying to change clinicians’ behaviour in those areas where there is already an identifiable research to practice gap. We have shown that by adapting the North of England guidelines for angina for local use, the uptake of aspirin for patients who have had an infarction can be considerably increased, at fairly low cost, in inner city practice. Evidence needs to be synthesised, and these guidelines are useful source documents, but we believe that the primary focus of guideline research must now shift to implementation of extant knowledge rather than summarising existing research. The challenge does not seem to be in improving the knowledge base, but in improving the utilisation of that knowledge within real life clinical situations.
Abstract 10880: Systemic Delivery of Bispecific Antibodies Promotes Stem Cell Homing and Improves Cardiac Function Post-Myocardial Infarction
Authors: Victoria Ballard, Tao Wang, Stephen C Lenhard, David J Figueroa, Weike Bao, Christian H James, Roberta E Bernard, Mary V Rambo, Gerald P McCafferty, Thil Batuwangala, Nadine K Clemo, Edward T Coulstock, Carrie Enever, Semra Kirk, Zahra Jawad-Alami, Beat M Jucker, James R Tunstead, Laurent Jespers, Erding Hu, Elena DeAngelis
Journal: Circulation (2010)

Background: Experimental studies have demonstrated the ability of bone marrow-derived stem cells to enhance cardiac repair and regeneration post-myocardial infarction (MI). However, clinical trials...
Media: Surgeon hits back at bullies in the press
Authors: S. Mayor
Journal: BMJ (1998)

It is impossible to miss the less than flattering picture of doctors in today's media, with headlines such as “Doctor murder enquiry widens” and “Hospital errors killing hundreds of new babies” regularly appearing in national newspapers. But has the reporting become a witch hunt?

Paediatric surgeon Simon Huddart, aged 41, who is clinical director of paediatric surgery at the University Hospital of Wales, Cardiff, has just emerged from a six month battle to clear his name after the Express newspaper splashed a story over its front page accusing him of cancelling an NHS operation on a 21 month old baby and then offering to do it privately. He was awarded substantial damages for libel when the newspaper accepted that the story was untrue and apologised. His story illustrates several lessons in dealing with the media: the importance of having witnesses to refute false accusations made during difficult confrontations, that trusts should speak to doctors involved in disputes before making any comment to the press, that talking to newspapers directly can sometimes be helpful, and that doctors can hit back at …