tbuckley/cabot-search huggingface dataset:
PCR detection of Mycobacterium paratuberculosis in Crohn's disease granulomas isolated by laser capture microdissection
Authors: P Ryan
Journal: Gut (2002)

<h3>Objectives</h3> Cardiovascular risk factors are prevalent in the population undergoing non-cardiac surgery. Changes in perioperative cardiovascular risk factor profiles over time are unknown. The objective of this study was to evaluate national trends in cardiovascular risk factors and atherosclerotic cardiovascular disease (ASCVD) among patients undergoing non-cardiac surgery. <h3>Methods</h3> Adults aged ≥45 years old who underwent non-cardiac surgery were identified using the US National Inpatient Sample from 2004 to 2013. The prevalence of traditional cardiovascular risk factors (hypertension, dyslipidaemia, diabetes mellitus, obesity and chronic kidney disease) and ASCVD (coronary artery disease, peripheral artery disease and prior stroke] were evaluated over time. <h3>Results</h3> A total of 10 581 621 hospitalisations for major non-cardiac surgery were identified. Between 2008 and 2013, ≥2 cardiovascular risk factors and ASCVD were present in 44.5% and 24.3% of cases, respectively. Over time, the prevalence of multiple (≥2) cardiovascular risk factors increased from 40.5% in 2008–2009 to 48.2% in 2012–2013, P&lt;0.001. The proportion of patients with coronary artery disease (17.2% in 2004–2005 vs 18.2% in 2012–2013, P&lt;0.001), peripheral artery disease (6.3% in 2004–2005 vs 7.4% in 2012–2013, P&lt;0.001) and prior stroke (3.5% in 2008–2009 vs 4.7% 2012–2013, P&lt;0.001) also increased over time. The proportion of patients with a modified Revised Cardiac Risk Index score ≥3 increased from 6.6% in 2008–2009 to 7.7% in 2012–2013 (P&lt;0.001). <h3>Conclusions</h3> Among patients undergoing major non-cardiac surgery, the burden of cardiovascular risk factors and the prevalence of ASCVD increased over time. Adverse trends in risk profiles require continued attention to improve perioperative cardiovascular outcomes.
Shaping cities for health: complexity and the planning of urban environments in the 21st century
Authors: Yvonne Rydin, Ana Bleahu, Michael Davies, Julio D Dávila, Sharon Friel, Giovanni De Grandis, Nora Groce, Pedro C Hallal, Ian Hamilton, Philippa Howden-Chapman, Ka-Man Lai, CJ Lim, Juliana Martins, David Osrin, Ian Ridley, Ian Scott, Myfanwy Taylor, Paul Wilkinson, James Wilson
Journal: The Lancet (2012)
Acute depletion of activated memory B cells involves the PD-1 pathway in rapidly progressing SIV-infected macaques
Authors: Kehmia Titanji, Vijayakumar Velu, Lakshmi Chennareddi, Matam Vijay-Kumar, Andrew T. Gewirtz, Gordon J. Freeman, Rama R. Amara
Journal: Journal of Clinical Investigation (2010)

Rapid progression to AIDS is a significant problem, especially in developing countries, where the majority of HIV-infected individuals reside. As rapid disease progression is also frequently observed in SIV-infected macaques, they represent a valuable tool to investigate the pathogenesis of this condition in humans. Here, we have shown that pathogenic SIV infection in rhesus macaques resulted in a rapid depletion (as early as week 2) of activated memory B (CD21-CD27+; mBAct) cells that was strongly associated with rapid disease progression. This depletion was progressive and sustained in rapid progressors, but less severe and transient in typical progressors. Because of the rapid and sustained depletion of mBAct cells, rapid progressors failed to develop SIV-specific Ab responses, showed a decline in non-SIV-specific Ab titers, and succumbed faster to intestinal bacterial infections. Depletion of mBAct cells was strongly associated with preferential depletion of mBAct cells expressing programmed death-1 (PD-1), and in vitro blockade of PD-1 improved their survival. Furthermore, in vivo PD-1 blockade in SIV-infected macaques enhanced Ab responses to non-SIV as well as SIV Ags. Our results identify depletion of mBAct cells as a very early predictor of rapid disease progression in pathogenic SIV infection and suggest an important role for the PD-1 pathway in depletion of mBAct cells and impaired humoral immune responses in SIV-infected macaques.
Phase III Placebo-Controlled Trial of Denileukin Diftitox for Patients With Cutaneous T-Cell Lymphoma
Authors: H. Miles Prince, Madeleine Duvic, Ann Martin, Wolfram Sterry, Chalid Assaf, Yijun Sun, David Straus, Mark Acosta, Andres Negro-Vilar
Journal: Journal of Clinical Oncology (2010)

PURPOSE This phase III, placebo-controlled, randomized trial was designed to investigate efficacy and safety of two doses of denileukin diftitox (DD; DAB(389)-interleukin-2 [IL-2]), a recombinant fusion protein targeting IL-2 receptor-expressing malignant T lymphocytes, in patients with stage IA to III, CD25 assay-positive cutaneous T-cell lymphoma (CTCL), including the mycosis fungoides and Sézary syndrome forms of the disease, who had received up to three prior therapies. The primary end point was overall response rate (ORR). PATIENTS AND METHODS Patients (N = 144) with biopsy-confirmed, CD25 assay-positive CTCL were randomly assigned to DD 9 microg/kg/d (n = 45), DD 18 microg/kg/d (n = 55), or placebo infusions (n = 44), administered for 5 consecutive days every 3 weeks for up to eight cycles. Patients were monitored for drug efficacy, clinical benefit, and safety of DD. RESULTS ORR was 44% for all participants treated with DD (n = 100; 10% complete response [CR] and 34% partial response [PR]) compared with 15.9% for placebo-treated patients (2% CR and 13.6% PR). ORR was higher in the 18 microg/kg/d group versus the 9 microg/kg/d group (49.1% v 37.8%, respectively), and both doses were significantly superior to placebo. Progression-free survival (PFS) was significantly longer (median, > 2 years) for both DD doses compared with placebo (median, 124 days; P < .001). Rates of moderately severe and severe adverse events (AEs) were slightly higher in the DD groups, whereas moderate and mild AEs were similar to placebo. No statistical differences were observed for drug-related serious AEs. CONCLUSION DD had a significant and durable effect on ORR and PFS with an acceptable safety profile in patients with early- and late-stage CTCL.
Prediction of Healing for Postoperative Diabetic Foot Wounds Based on Early Wound Area Progression
Authors: Lawrence A. Lavery, Sunni A. Barnes, Michael S. Keith, John W. Seaman, David G. Armstrong
Journal: Diabetes Care (2007)

To evaluate the probability of wound healing based on percentage of wound area reduction (PWAR) at 1 and 4 weeks in individuals with large, chronic, nonischemic diabetic foot wounds following partial foot amputation.Data from a 16-week randomized clinical trial (RCT) of 162 patients were analyzed to compare outcomes associated with negative-pressure wound therapy (NPWT) delivered through the V.A.C. Therapy System (Kinetic Concepts, San Antonio, TX) (n = 77) versus standard moist wound therapy (MWT) (n = 85). The 1- and 4-week regression models included 153 and 129 of the RCT patients, respectively.Early changes in PWAR were predictive of final healing at 16 weeks. Specifically, wounds that reached >or=15% PWAR at 1 week or >or=60% PWAR at 4 weeks had a 68 and 77% (respectively) probability of healing vs. a 31 and 30% probability if these wound area reductions were not achieved. Patients receiving NPWT were 2.5 times more likely to achieve both a 15% PWAR at 1 week and a 60% area reduction at 1 month (odds ratios 2.51 and 2.49, respectively) compared with those receiving MWT.Results of this study suggest that clinicians can calculate the PWAR of a wound as early as 1 week into treatment to predict the likelihood of healing at 16 weeks. This might also assist in identifying a rationale to reevaluate the wound and change wound therapies.
Embryonic Stem Cell–Derived CD166 <sup>+</sup> Precursors Develop Into Fully Functional Sinoatrial-Like Cells
Authors: Angela Scavone, Daniela Capilupo, Nausicaa Mazzocchi, Alessia Crespi, Stefano Zoia, Giulia Campostrini, Annalisa Bucchi, Raffaella Milanesi, Mirko Baruscotti, Sara Benedetti, Stefania Antonini, Graziella Messina, Dario DiFrancesco, Andrea Barbuti
Journal: Circulation Research (2013)

A cell-based biological pacemaker is based on the differentiation of stem cells and the selection of a population displaying the molecular and functional properties of native sinoatrial node (SAN) cardiomyocytes. So far, such selection has been hampered by the lack of proper markers. CD166 is specifically but transiently expressed in the mouse heart tube and sinus venosus, the prospective SAN.We have explored the possibility of using CD166 expression for isolating SAN progenitors from differentiating embryonic stem cells.We found that in embryonic day 10.5 mouse hearts, CD166 and HCN4, markers of the pacemaker tissue, are coexpressed. Sorting embryonic stem cells for CD166 expression at differentiation day 8 selects a population of pacemaker precursors. CD166+ cells express high levels of genes involved in SAN development (Tbx18, Tbx3, Isl-1, Shox2) and function (Cx30.2, HCN4, HCN1, CaV1.3) and low levels of ventricular genes (Cx43, Kv4.2, HCN2, Nkx2.5). In culture, CD166+ cells form an autorhythmic syncytium composed of cells morphologically similar to and with the electrophysiological properties of murine SAN myocytes. Isoproterenol increases (+57%) and acetylcholine decreases (-23%) the beating rate of CD166-selected cells, which express the β-adrenergic and muscarinic receptors. In cocultures, CD166-selected cells are able to pace neonatal ventricular myocytes at a rate faster than their own. Furthermore, CD166+ cells have lost pluripotency genes and do not form teratomas in vivo.We demonstrated for the first time the isolation of a nonteratogenic population of cardiac precursors able to mature and form a fully functional SAN-like tissue.
Microfabricated silicon microneedles for nonviral cutaneous gene delivery
Authors: F. Chabri, K. Bouris, T. Jones, D. Barrow, A. Hann, C. Allender, K. Brain, J. Birchall
Journal: British Journal of Dermatology (2004)

Background The skin represents an accessible somatic tissue for therapeutic gene transfer. The superficial lipophilic layer of the skin, the stratum corneum, however, constitutes a major obstacle to the cutaneous delivery of charged macromolecules such as DNA. Objectives To determine whether silicon‐based microneedles, microfabricated via a novel isotropic etching/BOSCH reaction process, could generate microchannels in the skin of sufficient dimensions to facilitate access of lipid : polycation : pDNA (LPD) nonviral gene therapy vectors. Methods Scanning electron microscopy was used to visualize the microconduits created in heat‐separated human epidermal sheets after application of the microneedles. Following confirmation of particle size and particle surface charge by photon correlation spectrocopy and microelectrophoresis, respectively, the diffusion of fluorescent polystyrene nanospheres and LPD complexes through heat‐separated human epidermal sheets was determined in vitro using a Franz‐type diffusion cell. In‐vitro cell culture with quantification by flow cytometry was used to determine gene expression in human keratinocytes (HaCaT cells). Results The diffusion of 100 nm diameter fluorescent polystyrene nanospheres, used as a readily quantifiable predictive model for LPD complexes, through epidermal sheets was significantly enhanced following membrane treatment with microneedles. The delivery of LPD complexes either into or through the membrane microchannels was also demonstrated. In both cases considerable interaction between the particles and the epidermal sheet was observed. In‐vitro cell culture was used to confirm that LPD complexes mediated efficient reporter gene expression in human keratinocytes in culture when formulated at the appropriate surface charge. Conclusions These studies demonstrate the utility of silicon microneedles in cutaneous gene delivery. Further studies are required to elucidate fully the influence of the physicochemical characteristics of gene therapy vectors, e.g. particle diameter and surface charge, on their diffusion through microchannels and to quantify gene expression in vivo.
Influence of Duration of Cholesterol Feeding on Esterification of Fatty Acids by Cell-Free Preparation of Pigeon Aorta
Authors: RICHARD W.ST. CLAIR, HUGH B. LOFLAND, THOMAS B. CLARKSON
Journal: Circulation Research (1970)

Influence of duration of cholesterol feeding on esterification of fatty acids and hydrolysis of cholesteryl esters was studied in cell-free preparations of aorta from White Carneau pigeons. Esterification of fatty acids required ATP and CoA; greater than 80% of the esterifying activity was located in the particulate fraction obtained by centrifugation at 105,000x g (after a preliminary centrifugation at 1000x g ). Fatty acids were incorporated most efficiently into phospholipid, primarily (82%) lecithin. Greater than 87% of the fatty acid was esterified at the 2-position. During 8 months of cholesterol feeding, incorporation of oleic acid into phospholipids and triglycerides increased relatively little (less than double that of controls); no changes were seen before 1 month. Esterification of oleic acid to cholesterol was increased after 2 weeks of cholesterol feeding (before gross lesions were seen), eventually reaching a maximum increase of 30- to 50-fold. Cholesterol was esterified by transfer of fatty acyl-CoA to cholesterol, a mechanism similar to that described for liver and adrenal cortex. Little if any cholesterol esterification occurred when lecithin labeled at the 2-position with oleic acid-l- 14 C was used as substrate. The relationship between duration of cholesterol feeding and hydrolysis of cholesteryl oleate could not be evaluated since results depend directly on an unknown extent of equilibration of substrate with pre-existing cholesteryl ester pools.
Impact of Prolonged Exacerbation Recovery in Chronic Obstructive Pulmonary Disease
Authors: Gavin C. Donaldson, Martin Law, Beverly Kowlessar, Richa Singh, Simon E. Brill, James P. Allinson, Jadwiga A. Wedzicha
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Exacerbations are important and heterogeneous events in the natural history of chronic obstructive pulmonary disease (COPD).Objectives: To examine the consequences of prolonged exacerbation recovery in patients with COPD.Methods: A cohort of 384 patients with COPD (FEV1 % predicted 45.8 [SD, 16.6] and a median exacerbation rate of 2.13 per year [interquartile range, 1.0–3.2]) were followed for 1,039 days (interquartile range, 660–1,814) between October 1995 and January 2013. Patients recorded daily worsening of respiratory symptoms and peak expiratory flow (PEF), and when stable underwent spirometry every 3 months, and completed the St. George's Respiratory Questionnaire annually. Exacerbations were diagnosed as 2 consecutive days with one major symptom plus another respiratory symptom. Exacerbation duration was defined as the time from onset to the day preceding 2 consecutive symptom-free days and recovery in PEF as return to preexacerbation levels.Measurements and Main Results: A total of 351 patients had one or more exacerbations. Patients with a longer symptom duration (mean, 14.5 d) had a worse St. George's Respiratory Questionnaire total score (0.2 units per 1 day; P = 0.040). A longer symptomatic duration was associated with a shorter interval between exacerbation recovery and onset of the next exacerbation (hazard ratio, 1.004; P = 0.013). For 257 (7.3%) exacerbations, PEF did not recover within 99 days. These exacerbations were associated with symptoms of a viral infection (cold and sore throat). Patients with these nonrecovered exacerbations showed a 10.8 ml/yr (P < 0.001) faster decline in FEV1.Conclusions: Prolonged exacerbation symptomatic duration is associated with poorer health status and a greater risk of a new event. Exacerbations where lung function does not recover are associated with symptoms of viral infections and accelerated decline in FEV1.
PTU-211 Patient preparation prior to gastroscopy: a UK wide survey
Authors: J Callaghan, J Neale, P Boger, P Patel
Journal: Gut (2012)

Introduction Background: Optimal patient preparation for colonoscopy is shown to improve polyp detection in the colon. In Japan, it is widely accepted practice to administer a mucolytic agent prior to gastroscopy to improve visualisation of the upper gastrointestinal tract. There is a paucity of robust UK studies which describe optimal methods of preparation prior to gastroscopy. The current variations in UK practice have not been quantified. Aims : To investigate current practice in patient preparation prior to gastroscopy across the UK. Methods A list of all Hospitals in the UK was obtained from the JAG website (391). Hospitals that did not perform endoscopy were excluded (14), as were Children's Hospitals (5) and private hospitals (165). The number of hospitals included was 207. A structured telephone survey was conducted with each endoscopy unit. The method of preparation prior to gastroscopy was established. Results 193 (93%) endoscopy units responded to the survey. 11 (5%) endoscopy units declined to participate in the survey and 3 (2%) of endoscopy units did not respond. Preparation prior to gastroscopy (%) included: No hospital used a mucolytic drink for routine gastroscopy cases. Conclusion Current gastroscopy preparation regimes vary across the UK. Future studies should evaluate which preparation regime provides the best possible visualisation of the upper gastrointestinal tract. Competing interests None declared.
Is air travel safe for those with lung disease?
Authors: R. K. Coker, R. J. Shiner, M. R. Partridge
Journal: European Respiratory Journal (2007)

Airlines commonly report respiratory in-flight emergencies; flight outcomes have not been examined prospectively in large numbers of respiratory patients. The current authors conducted a prospective, observational study of flight outcomes in this group. UK respiratory specialists were invited to recruit patients planning air travel. Centres undertook their usual pre-flight assessment. Within 2 weeks of returning, patients completed a questionnaire documenting symptoms, in-flight oxygen use and unscheduled healthcare use. In total, 616 patients were recruited. Of these, 500 (81%) returned questionnaires. The most common diagnoses were airway (54%) and diffuse parenchymal lung disease (23%). In total, 12 patients died, seven before flying and five within 1 month. Pre-flight assessment included oximetry (96%), spirometry (95%), hypoxic challenge (45%) and walk test (10%). Of the patients, 11% did not fly. In those who flew, unscheduled respiratory healthcare use increased from 9% in the 4 weeks prior to travel to 19% in the 4 weeks after travel. However, when compared with self-reported data during the preceding year, medical consultations increased by just 2%. In patients flying after careful respiratory specialist assessment, commercial air travel appears generally safe.
Xenografts of Primary Human Prostatic Carcinoma
Authors: T. G. Pretlow, S. R. Wolman, M. A. Micale, R. J. Pelley, E. D. Kursh, M. I. Resnick, D. R. Bodner, J. W. Jacobberger, C. M. Delmoro, J. M. Giaconia, T. P. Pretlow
Journal: JNCI Journal of the National Cancer Institute (1993)

Prostatic carcinoma is both the most common invasive cancer and the second most common cause of cancer deaths in men in the United States. Before 1991, attempts to propagate prostatic carcinoma from primary tumors for periods longer than 3 months were unsuccessful in vivo and in vitro with rare exceptions. In 1991, we reported establishment of slowly growing tumors for six of 10 human primary prostatic carcinomas approximately 2-6 months after transplantation. However, none of the tumors were larger than 5 mm or serially transplantable.Our purpose in this study was to determine whether human primary prostatic carcinoma could be grown as serially transplantable xenografts.Cells from primary prostatic carcinomas obtained from transurethral prostatic resections or total prostatectomies in 20 patients were injected subcutaneously into male nude mice on the day of surgery. Sustained-release testosterone pellets were placed subcutaneously in the mice 2-24 days before transplantation of tumors and at intervals of 10-12 weeks. Serial transplantations in subsequent generations of mice were carried out by similar methods. Chromosome analysis was performed on six tumors.Six of 20 primary prostatic carcinomas have grown sufficiently to permit serial transplantation into second mice; four have been documented histopathologically in the second mouse and serially transplanted into three or more successive mice. When a single primary tumor was injected into several mice by the same procedure, tumors failed to grow in some recipients but became serially transplantable in others. Growth of these tumors is slow and irregular, with frequent regressions. Short-term cultures of 10 tumors, eight of which were injected into mice in parallel, were initiated on the day of surgery; CWR31, which was successfully transplanted serially, exhibited only aberrant metaphases and showed clonal, chromosomal changes in culture. Including CWR31, three of the six tumors for which chromosomal analysis was successful contained clonal aberrations. Preliminary studies of SCID (severe combined immunodeficient) mice suggest that they are not superior to nude mice for establishment of serially transplantable prostatic carcinoma xenografts.A proportion of human primary prostatic carcinomas can be grown as xenografts. Four new serially transplantable xenografts (CWR21, CWR31, CWR91, and CWR22) are currently propagated in our laboratory, a resource that was not previously available.Our experience suggests that the most important factor in serial transplantation is the collaboration of urologists and pathologists in expediting placement of the tumor in cold saline, examination of the frozen section, and transplantation.
Nutritional Scientist or Biochemist?
Authors: J.W. Suttie
Journal: Annual Review of Nutrition (2011)

When invited by the editors to provide a prefatory article for the Annual Review of Nutrition, I attempted to decide what might be unique about my experiences as a nutritional biochemist. Although a large proportion of contemporary nutritional scientists were trained as biochemists, the impact of the historical research efforts related to nutrition within the Biochemistry Department at the University of Wisconsin 50 to 60 years ago was, I think, unique, and I have tried to summarize that historical focus. My scientific training was rather standard, but I have tried to review the two major, but greatly different, areas of research that I have been involved in over my career: inorganic fluorides as an industrial pollutant and the metabolic role of vitamin K. I have also had the opportunity to become involved with the activities of the societies representing the nutritional sciences (American Society for Nutrition), biochemistry (American Society for Biochemistry and Molecular Biology), Federation of American Societies for Experimental Biology, the Food and Nutrition Board, the Board on Agriculture and Natural Resources, and the U.S. Department of Agriculture National Agricultural Research, Extension, Education, and Economics. These interactions can be productive or frustrating but are always time-consuming.