tbuckley/cabot-search huggingface dataset:
Right Ventricular Enlargement on Chest Computed Tomography
Authors: U. Joseph Schoepf, Nils Kucher, Florian Kipfmueller, Rene Quiroz, Philip Costello, Samuel Z. Goldhaber
Journal: Circulation (2004)

In patients with acute pulmonary embolism (PE), rapid and accurate risk assessment is paramount in selecting the appropriate treatment strategy. Right ventricular (RV) enlargement on chest CT has previously been shown to correlate with an unstable hospital course, but its role as a predictor of death is unknown.We evaluated 431 consecutive patients (mean age, 59+/-16 years; 55% women) with acute PE confirmed by multidetector-row chest CT. With the use of multiplanar reformats of axial CT data, CT 4-chamber (4-CH) views were reconstructed and right and left ventricular dimensions (RV(D), LV(D)) were measured. RV enlargement, defined as RV(D)/LV(D) >0.9, was present in 276 (64.0%; 95% CI, 59.5% to 68.6%) patients. Thirty-day mortality rate was 15.6% (95% CI, 11.3% to 19.9%) in patients with and 7.7% (95% CI, 3.5% to 12.0%) without RV enlargement (log rank, P=0.018). The hazard ratio of RV(D)/LV(D) >0.9 for predicting 30-day death was 3.36 (95% CI, 1.13 to 9.97; P=0.029). On multivariable analysis, RV enlargement predicted 30-day death (hazard ratio, 5.17; 95% CI, 1.63 to 16.35; P=0.005) after adjusting for pneumonia (hazard ratio, 2.95; 95% CI, 1.19 to 3.83; P=0.002), cancer (hazard ratio, 2.13; 95% CI, 1.19 to 3.83; P=0.011), chronic lung disease (hazard ratio, 2.00; 95% CI, 1.04 to 3.86; P=0.039), and age (hazard ratio, 1.03; 95% CI, 1.01 to 1.05; P=0.005).In patients with acute PE, RV enlargement on reconstructed CT 4-CH view helps predict early death.
Human visceral afferent recordings: preliminary report
Authors: M. Peiris, D. C. Bulmer, M. D. Baker, G. Boundouki, S. Sinha, A. Hobson, K. Lee, Q. Aziz, C. H. Knowles
Journal: Gut (2010)

<h3>Background</h3> Conditions characterised by chronic visceral pain represent a significant healthcare burden with limited treatment options. While animal models have provided insights into potential mechanisms of visceral nociception and identified candidate drug targets, these have not translated into successful treatments in humans. <h3>Objective</h3> To develop an in vitro afferent nerve preparation using surgically excised freshly isolated human colon and vermiform appendix-mesentery tissues. <h3>Methods</h3> Non-inflamed appendix (n=18) and colon (n=9) were collected from patients undergoing right and left hemicolectomy. Electrophysiological recordings were made from mesenteric nerves and the tissue stimulated chemically and mechanically. <h3>Results</h3> Ongoing neuronal activity was sparse and where units occurred peak firing rates were: colon (2.0±0.4 spikes/s, n=4) and appendix (2.4±0.6 spikes/s, n=9). Afferent nerves innervating the appendix responded with a significant increase in activity following stimulation with inflammatory mediators (73±10.6 vs 3.0±0.3 spikes/s, n=6, p&lt;0.001, inflammatory mediator vs baseline) and capsaicin (63±15.8 vs 2±0.3 spikes/s, n=3, p&lt;0.001, capsaicin vs buffer). Afferent nerves innervating the colon responded with increased activity to blunt probing of the serosal surface. <h3>Conclusions</h3> This first-in-human study demonstrates afferent nerve recordings from human gut tissue ex vivo and shows that tissue may be stimulated both chemically and mechanically to study neuronal responses. Collectively, the results provide preliminary evidence to validate this in vitro human tissue model as one that may aid future disease mechanistic studies and candidate drug testing.
CD4−CD8− T cells control intracellular bacterial infections both in vitro and in vivo
Authors: Siobhán C. Cowley, Elizabeth Hamilton, Jeffrey A. Frelinger, Jie Su, James Forman, Karen L. Elkins
Journal: The Journal of Experimental Medicine (2005)

Memory T cells, including the well-known CD4(+) and CD8(+) T cells, are central components of the acquired immune system and are the basis for successful vaccination. After infection, CD4(+) and CD8(+) T cells expand into effector cells, and then differentiate into long-lived memory cells. We show that a rare population of CD4(-)CD8(-)CD3(+)alphabeta(+)gammadelta(-)NK1.1(-) T cells has similar functions. These cells potently and specifically inhibit the growth of the intracellular bacteria Mycobacterium tuberculosis (M. tb.) or Francisella tularensis Live Vaccine Strain (LVS) in macrophages in vitro, promote survival of mice infected with these organisms in vivo, and adoptively transfer immunity to F. tularensis LVS. Furthermore, these cells expand in the spleens of mice infected with M. tb. or F. tularensis LVS, and then acquire a memory cell phenotype. Thus, CD4(-)CD8(-) T cells have a role in the control of intracellular infection and may contribute to successful vaccination.
GP numbers are not shrinking but demand is swallowing the extra workforce, MPs told
Authors: Adrian O’Dowd
Journal: BMJ (2015)

The number of new GPs joining general practice is steady and rising slightly despite widespread perceptions that the workforce is shrinking, MPs have been told.

However, rising demand from a growing older population has meant that the supply is effectively being “mopped up,” workforce experts told the parliamentary health committee during the first evidence session for its inquiry into primary care held on 3 November.

The inquiry is focusing on the recommendations from the Primary Care Workforce Commission report, which was published in July.1 These recommendations included running pilots of GPs communicating with patients vie email; greater collaboration between organisations; and the involvement of a broader range of staff in the delivery of healthcare, such as pharmacists, physician associates, and medical assistants.

MPs asked about the government’s plans to have an additional 5000 whole time equivalent doctors working …
Influencing the practice and outcome in acute upper gastrointestinal haemorrhage
Authors: T A Rockall, R F A Logan, H B Devlin, T C Northfield
Journal: Gut (1997)

Aims — To assess changes in practice and outcome in acute upper gastrointestinal haemorrhage following the feedback of data, the reemphasis of national guidelines, and specific recommendations following an initial survey. Design — A prospective, multicentre, audit cycle. Forty five hospitals from three health regions participed in two phases of the audit cycle. Patients — Phase I: 2332 patients with acute upper gastrointestinal haemorrhage; phase II: 1625 patients with upper gastrointestinal haemorrhage. Methods — Patients were evaluated with respect to management (with reference to the recommendations in the national guidelines), mortality, and length of hospital stay. Results — Following the distribution of data from the first phase of the National Audit and the formulation of specific recommendations for improving practice, the proportion of hospitals with local guidelines or protocols for the management of upper gastrointestinal haemorrhage rose from 71% (32/45) to 91% (41/45); 12 of the 32 hospitals with guidelines during the first phase revised their guidelines following the initial survey. There was a small but significant increase in the proportion of all patients who underwent endoscopy (from 81% to 86%), the proportion who underwent endoscopy within 24 hours of admission (from 50% to 56%), and the use of central venous pressure monitoring in patients with organ failure requiring blood transfusion or those with profound shock (from 30% to 43%). There was, however, no change in the use of high dependency beds or joint medical/surgical management in high risk cases. There was no significant change in crude or risk standardised mortality (13.4% in the first phase and 14.4% in the second phase). Conclusions — Although many of the participating hospitals have made efforts to improve practice by producing or updating guidelines or protocols, there has been only a small demonstrable change in some areas of practice during the National Audit. The failure to detect any improvement in mortality may reflect this lack of change of practice, but may also reflect the fact that a large proportion of the deaths in this unselected study are not preventable; only a very large study could hope to demonstrate a significant change out of the context of a clinical trial.
Changes in oxidative stress parameters and antioxidant status in lung cancer: Western blot analysis of nitrotyrosine and protein carbonyls content
Authors: Gulcan G. Korkmaz, Berrin B. Inal, Gonenc M. Ortakoylu, Hulya Irmak, Asuman A. Kara, Remise Gelisgen, Ozcan Ogurlu, Hafize Uzun
Journal: European Respiratory Journal (2013)

Background: The source of many diseases, including tumours, lies in an increased generation of reactive oxygen species resulting in an oxidative stress. We investigated the relationships between advanced protein oxidation products(AOPPs), nitrotyrosine(NT), protein carbonyls(PCO) content, total antioxidant capacity(TAC) and the pro-oxidant-antioxidant balance(PAB) in patients with lung cancer. Methods: A total of 14 age-matched healthy controls, 14 subjects with non-lung cancer pulmonary disease, and 41 patients with lung cancer were included in this study. Spectrophotometry was used to examine plasma AOPP, serum TAC and PAB, while serum PCO and NT were assessed with western blot analysis. Results: A significant difference in AOPP levels were found between patients and controls(p<0.01). Also, there was a highly significant difference in NT levels between patients and controls(p<0.001). PAB showed negative correlation with albumin(r=-0.340;p=0.011) and positive correlation with CRP(r=0.342;p=0.011). AOPP, albumin, gender and smoking were the significant independent variables found by Backward Stepwise multiple logistic regression (MLR) analysis method. MLR analysis revealed that AOPP was the variable that had a significant effect on lung cancer[(p=0.006;OR=1.074;(95% CI)(1.020-1.131)]. Conclusions: The use of non-invasive diagnostic biochemical parameters would represent a very important contribution to our diagnostic armamentarium in lung cancer, c o nsidering the high incidence of this deadly disease. In this regard, AOPP and NT levels have appeared to play a prominent role, although further studies are certainly warranted.
Antitumor activity of DAB389 IL-2 fusion toxin in mycosis fungoides
Authors: Mansoor N. Saleh, C.F. LeMaistre, Timothy M. Kuzel, Francine Foss, Leonidas C. Platanias, Gary Schwartz, Mark Ratain, Alain Rook, Cesar O. Freytes, Fiona Craig, James Reuben, Mitchell W. Sams, Jean C. Nichols
Journal: Journal of the American Academy of Dermatology (1998)
Apoptosis Inhibitor ARC Promotes Breast Tumorigenesis, Metastasis, and Chemoresistance
Authors: Christina M. Medina-Ramirez, Sumanta Goswami, Tatiana Smirnova, Daniel Bamira, Benjamin Benson, Neal Ferrick, Jeffrey Segall, Jeffrey W. Pollard, Richard N. Kitsis
Journal: Cancer Research (2011)

Abstract Apoptosis repressor with caspase recruitment domain (ARC) inhibits both death receptor- and mitochondrial/ER-mediated pathways of apoptosis. Although expressed mainly in terminally differentiated cells, ARC is markedly upregulated in a variety of human cancers, where its potential contributions have not yet been defined. In this study, we provide evidence of multiple critical pathophysiologic functions for ARC in breast carcinogenesis. In the polyoma middle T-antigen (PyMT) transgenic mouse model of breast cancer, in which endogenous ARC is strongly upregulated, deletion of the ARC-encoding gene nol3 decreased primary tumor burden without affecting tumor onset or multiplicity. More notably, ARC deficiency also limited tumor cell invasion and the number of circulating cancer cells, markedly reducing the number of lung metastases. Conversely, ectopic overexpression of ARC in a PyMT-derived metastatic breast cancer cell line increased invasion in vitro and lung metastasis in vivo. We confirmed these results in a humanized orthotopic model based on MDA-MB-231-derived LM2 metastatic breast cancer cells, in which RNAi-mediated knockdown of ARC levels was shown to reduce tumor volume, local invasion, and lung metastases. Lastly, we found that endogenous levels of ARC conferred chemoresistance in primary tumors and invading cell populations. Our results establish that ARC promotes breast carcinogenesis by driving primary tumor growth, invasion, and metastasis as well as by promoting chemoresistance in invasive cells. Cancer Res; 71(24); 7705–15. ©2011 AACR.
S40 Early experience of endobronchial ultrasound-miniprobe (EBUS-MP) for investigation of peripheral pulmonary mass lesions
Authors: J. F. Tiernan, W. Wallace, K. M. Skwarski
Journal: Thorax (2010)

<h3>Introduction</h3> Peripheral pulmonary mass lesions are common findings in respiratory medicine. The frequency of detection of such lesions is rising with increasing availability of radiological imaging techniques. Their aetiology may need to be established by tissue sampling to facilitate appropriate management, for example, suspected malignancy. Traditional investigations include CT-guided biopsy, bronchoscopic biopsy, endoscopic ultrasound with fine needle aspiration (EBUS/EUS) and surgical intervention. Each modality has potential complications, for example, pneumothorax following CT-guided biopsy. Endoscopic ultrasound miniprobe is established as a valuable tool, particularly in the staging of early GI tumours and in extraductal visualisation of the biliary tract. EBUS-MP has been used for qualitative assessment of bronchial mural structures in lung transplant recipients but little is known about the role of EBUS-MP sampling of peripheral pulmonary mass lesions. The purpose of this paper is to demonstrate our experience with this technique to date. <h3>Methods</h3> All EBUS-MP procedures were carried out over a 6-month period in a tertiary respiratory centre. Patients were referred for suspected malignancy. All procedures were undertaken by the same consultant bronchoscopist, assisted by a respiratory trainee. An Olympus UM-S20-17S 1.7 mm Miniprobe<sup>®</sup> was identify the target lesion. Samples (biopsies or endobronchial brushings) were then taken from the identified subsegmental bronchus. Each case was subsequently reviewed with respect to diagnostic rate, subsequent management, complications and potential alternative investigations to EBUS-MP. <h3>Results</h3> 24 EBUS-MP procedures were performed on 22 patients (Age range 53–82 years (mean 70.4 years)). FEV1 ranged from 0.8 L to 2.9 L. 20 of 22 CT-identified lesions (14–60 mm) were visualised with EBUS-MP. No complications occurred in study population. Abstract S40 Figure 1 shows detailed outcomes for EBUS-MP. <h3>Conclusions</h3> EBUS-MP is a novel technique in bronchoscopy. Our early experience has demonstrated some potential usefulness of the procedure, allowing good visualisation of lesions. No complications have occurred to date. We believe that EBUS-MP sampling may have a role in investigation of peripheral pulmonary mass lesions. In a well selected cohort of patients it appears to be a safe alternative to CT-guided biopsy.
Systematic review of the cost effectiveness of prophylactic treatments in the prevention of gastropathy in patients with rheumatoid arthritis or osteoarthritis taking non-steroidal anti-inflammatory drugs
Authors: H. E M van Dieten
Journal: Annals of the Rheumatic Diseases (2000)

A systematic review on the cost effectiveness of prophylactic treatments of non-steroidal anti-inflammatory drug (NSAID) induced gastropathy in patients with osteoarthritis or rheumatoid arthritis was conducted. Two reviewers conducted the literature search and the review. Both full and partial economic evaluations published in English, Dutch, or German were included. The criteria list published in the textbook of Drummond was used to determine the quality of the economic evaluations. The methodological quality of three randomised controlled trials (RCTs) in which the economic evaluations obtained probability estimates of NSAID induced gastropathy and adverse events was assessed by a list of internal validity criteria. The conclusions were based on a rating system consisting of four levels of evidence. Ten economic evaluations were included; three were based on RCTs. All evaluations studied misoprostol as prophylactic treatment: in one evaluation misoprostol was studied as a fixed component in a combination with diclofenac (Arthrotec). All economic evaluations comprised analytical studies containing a decision tree. The three trials were of high methodological quality. Nine economic evaluations were considered high quality and one economic evaluation was considered of low methodological quality. There is strong evidence (level "A") that the use of misoprostol for the prevention of NSAID induced gastropathy is cost effective, and limited evidence (level "C") that the use of Arthrotec is cost effective. Although the levels of evidence used in this review are arbitrary, it is believed that a qualitative analysis is useful: quantitative analyses in this field are hampered by the heterogeneity of economic evaluations. Existing criteria to evaluate the methodological quality of economic evaluations may need refinement for use in systematic reviews.
Inhibiting MicroRNA-192 Ameliorates Renal Fibrosis in Diabetic Nephropathy
Authors: Sumanth Putta, Linda Lanting, Guangdong Sun, Gregory Lawson, Mitsuo Kato, Rama Natarajan
Journal: Journal of the American Society of Nephrology (2012)

TGF-β1 upregulates microRNA-192 (miR-192) in cultured glomerular mesangial cells and in glomeruli from diabetic mice. miR-192 not only increases collagen expression by targeting the E-box repressors Zeb1/2 but also modulates other renal miRNAs, suggesting that it may be a therapeutic target for diabetic nephropathy. We evaluated the efficacy of a locked nucleic acid (LNA)-modified inhibitor of miR-192, designated LNA-anti-miR-192, in mouse models of diabetic nephropathy. LNA-anti-miR-192 significantly reduced levels of miR-192, but not miR-194, in kidneys of both normal and streptozotocin-induced diabetic mice. In the kidneys of diabetic mice, inhibition of miR-192 significantly increased Zeb1/2 and decreased gene expression of collagen, TGF-β, and fibronectin; immunostaining confirmed the downregulation of these mediators of renal fibrosis. Furthermore, LNA-anti-miR-192 attenuated proteinuria in these diabetic mice. In summary, the specific reduction of renal miR-192 decreases renal fibrosis and improves proteinuria, lending support for the possibility of an anti-miRNA-based translational approach to the treatment of diabetic nephropathy.
Vitamin E attenuates the injurious effects of bioactive phospholipids on human ciliated epithelium<i>in vitro</i>
Authors: C. Feldman, R. Anderson, A.J. Theron, H.C. Steel, C.E.J. van Rensburg, P.J. Cole, R. Wilson
Journal: European Respiratory Journal (2001)

Bioactive phospholipids (PL), particularly lysophosphatidylcholine (LPC), are being increasingly implicated in the pathogenesis of various acute and chronic inflammatory disorders, particularly those of the airways, while there is emerging evidence that vitamin E may function as a natural antagonist of these lipid mediators of inflammation. The aims of this study were to document the effects of vitamin E on the inhibition of ciliary beating and damage to structural integrity of human ciliated epithelium induced by the PL, platelet-activating factor (PAF), lyso-PAF and LPC in vitro in relation to the anti-oxidative and membrane-stabilizing properties of the vitamin. Ciliary beat frequency was measured by a phototransistor technique, and damage to structural integrity assessed by a visual-scoring index, while superoxide production by polymorphonuclear leukocytes and membrane-stabilizing potential were measured using lucigenin-enhanced chemiluminescence and haemolytic procedures, respectively. All three PL caused inhibition of ciliary beating and structural damage to human ciliated epithelium by membrane-directed cytotoxic mechanisms, which were potentiated by human polymorphonuclear leukocytes due to induction of oxidant-mediated injury. Both direct and phagocyte-inflicted epithelial injury was attenuated by vitamin E. In haemolytic and chemiluminescence assays, vitamin E neutralized both the membrane-destabilizing and pro-oxidative actions of all three PL, while spectrophotometric analysis of mixtures of vitamin E with PAF, lyso-PAF and LPC revealed alterations in peak intensity, as well as peak shifts, indicative of physicochemical interactions between the vitamin and the PL. Vitamin E status may be a determinant of susceptibility to phospholipid-mediated airway inflammation and damage.
Collagenolytic Activity of Rabbit V&lt;sub&gt;2&lt;/sub&gt; Carcinoma Implanted in the Nude Mouse&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: C Biswas, K J Bloch, J Gross
Journal: JNCI Journal of the National Cancer Institute (1982)

The relative contribution of host cells and tumor cells to the production of collagenase and its regulation during tumorigenesis were studied with the use of a heterologous rabbit tumor-nude mouse host system. The V2 carcinoma, a malignant neoplasm of the New Zealand White rabbit, behaved as a nonmetastasizing, noninvasive tumor when implanted and grown in the inbred Swiss albino nude mouse. The extracts from both tumors contained similar levels of collagenase. Tumor explants also released enzyme into culture medium in both cases, but the rabbit tumor produced approximately 10 times more collagenase than the nude mouse. Freeze-thawing of the explants or treatment with cycloheximide markedly inhibited the appearance of enzyme in the medium from the rabbit tumor but not from the nude mouse tumor. The relative proportions of mouse- and rabbit-derived collagenase in the nude mouse tumor extracts and culture medium were determined with the use of antibodies specific for rabbit V2 tumor and mouse bone collagenases. Approximately 70% of the nude mouse tumor enzyme was derived from the rabbit tumor, and approximately 30% was derived from the mouse host. These findings indicate that the former might represent stored enzyme carried over during tumor transplantation into the nude mouse, whereas the latter might have originated from stimulation of host cells during tumorigenesis.
Physical therapies in sport and exercise
Authors: D B Kenneally
Journal: British Journal of Sports Medicine (2005)

Edited by G S Kolt, L Snyder-Mackler. Published by Churchill Livingstone, 2003, £60.00, hardcover, pp 623. ISBN 0443071543

Physical therapies in sports and exercise , as the name suggests, is sports medicine from a physical therapy perspective. As with all of these types of book, it tries to cover everything, draws on clinicians and researchers from around the globe, and succeeds well in giving a general guide. It is a mix of strong and concise anatomical review, general concepts within sports and exercise, regional injury management, other active groups, and a section on medical issues.

The editors make the point early on that there is a dearth of evidence for the techniques and approaches we use in physical therapies within sport. The stated aim is to “provide a logical approach to the management of sport …