tbuckley/cabot-search huggingface dataset:
Sensitivity and specificity of St. George's Respiratory Questionnaire in predicting low lung function in patients treated for pulmonary tuberculosis
Authors: Mikhail Chushkin, Elena Bogorodskaya, Valentina Aksenova, Vadim Koroev, Sergey Mandrykin, Dmitriy Zhutikov, Eduard Tikhokhod, Sergey Smerdin
Journal: European Respiratory Journal (2012)

Tuberculosis is associated with frequent pulmonary impairment. This supports performance of pulmonary function tests in the course of treatment and after a cure but until now pulmonary function testing had not been included in tuberculosis treatment guidelines. The aim of the study was to assess the usefulness St. George's Respiratory Questionnaire (SGRQ) for predicting low lung function in patients after treatment of pulmonary tuberculosis.

Methods: we investigated 226 patients older than 40 years who were cured for pulmonary tuberculosis (145 males and 81 females). Quality of Life was studied by SGRQ. Pulmonary function was studied by spirometry. Receiver Operating Characteristic (ROC) curve analysis was used for assessment of sensitivity and specificity.

Results: Out of 226 patients, 97 (42,9%) had low lung function (FEV1 < 80% predicted). According to ATS/ERS criteria we classified 8,8% of subjects as having mild impairment; 20,8% of subjects as having moderate impairment; and 13,3% of subjects as having severe impairment. According ROC curve analysis for low lung function, when 29% of Total SGRQ score was chosen as the cut-off, the sensitivity, specificity, positive value and negative value were 57.7%, 83%, 72%, and 72%, respectively. Area under the ROC curve (AUC) was 0,75 (95% confidential interval [CI] 0,69 to 0.81; p<0.001). AUC was a bit bigger in male than in female (0,79 vs 0,69).

Conclusion: Total SGRQ of 29% may be the best cut-off in low pulmonary function detection. Higher Total SGRQ score was associated with higher probability of low pulmonary function.
CD1c bypasses lysosomes to present a lipopeptide antigen with 12 amino acids
Authors: Ildiko Van Rhijn, David C. Young, Annemieke De Jong, Jenny Vazquez, Tan-Yun Cheng, Rahul Talekar, Duarte C. Barral, Luis León, Michael B. Brenner, Joel T. Katz, Richard Riese, Ruth M. Ruprecht, Peter B. O'Connor, Catherine E. Costello, Steven A. Porcelli, Volker Briken, D. Branch Moody
Journal: The Journal of Experimental Medicine (2009)

The recent discovery of dideoxymycobactin (DDM) as a ligand for CD1a demonstrates how a nonribosomal lipopeptide antigen is presented to T cells. DDM contains an unusual acylation motif and a peptide sequence present only in mycobacteria, but its discovery raises the possibility that ribosomally produced viral or mammalian proteins that commonly undergo lipidation might also function as antigens. To test this, we measured T cell responses to synthetic acylpeptides that mimic lipoproteins produced by cells and viruses. CD1c presented an N-acyl glycine dodecamer peptide (lipo-12) to human T cells, and the response was specific for the acyl linkage as well as the peptide length and sequence. Thus, CD1c represents the second member of the CD1 family to present lipopeptides. lipo-12 was efficiently recognized when presented by intact cells, and unlike DDM, it was inactivated by proteases and augmented by protease inhibitors. Although lysosomes often promote antigen presentation by CD1, rerouting CD1c to lysosomes by mutating CD1 tail sequences caused reduction in lipo-12 presentation. Thus, although certain antigens require antigen processing in lysosomes, others are destroyed there, providing a hypothesis for the evolutionary conservation of large CD1 families containing isoforms that survey early endosomal pathways.
Elevated Plasma YKL-40 Predicts Increased Risk of Gastrointestinal Cancer and Decreased Survival After Any Cancer Diagnosis in the General Population
Authors: Julia S. Johansen, Stig E. Bojesen, Anne K. Mylin, Ruth Frikke-Schmidt, Paul A. Price, Børge G. Nordestgaard
Journal: Journal of Clinical Oncology (2008)

Elevated plasma YKL-40 is a biomarker of poor prognosis in cancer patients. We tested the hypotheses that elevated plasma YKL-40 predicts risk of cancer as well as survival after a cancer diagnosis in the general population.A prospective cohort study of 8,899 subjects (20 to 95 years) from the Danish general population, the Copenhagen City Heart Study, observed for 11 years for cancer incidence and 14 years for death: 1,432 participants had a first incident cancer, 968 of these died. Hazard ratios (HRs) for cancer events and death after events according to plasma YKL-40 in sex and 10 years age percentile categories: 0% to 33%, 34% to 66%, 67% to 90%, 91% to 95%, and 96% to 100%.The cumulative incidence of gastrointestinal cancer increased with increasing YKL-40 (trend P < .0001). Multifactorially adjusted HRs for gastrointestinal cancer were 1.0 (95% CI, 0.7 to 1.5) for YKL-40 in category 34% to 66%, 1.5 for 67% to 90% (95% CI, 1.0 to 2.3), 2.4 for 91% to 95%, (95% CI, 1.3 to 4.6), and 3.4 for 96% to 100% (95% CI, 1.9 to 6.1) versus YKL-40 category 0% to 33% (P < .0001). Participants with any cancer event and YKL-40 category 91% to 100% had a median survival time after the diagnosis of 1 year versus 4 years in participants with YKL-40 category 0% to 33% (P < .0001). Corresponding values for gastrointestinal cancer were 6 months versus 1 year (P = .007). Multifactorially adjusted HRs for early death were 1.8 (95% CI, 1.3 to 2.5; P < .0001) after any cancer and 2.4 (95% CI, 1.3 to 4.3; P = .005) after gastrointestinal cancer in participants with YKL-40 category 91% to 100% versus 0% to 33%.In the general population, elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis.
Selective Targeting of Antitumor Immune Responses with Engineered Live-Attenuated <i>Listeria monocytogenes</i>
Authors: Kiyoshi Yoshimura, Ajay Jain, Heather E. Allen, Lindsay S. Laird, Christina Y. Chia, Sowmya Ravi, Dirk G. Brockstedt, Martin A. Giedlin, Keith S. Bahjat, Meredith L. Leong, Jill E. Slansky, David N. Cook, Thomas W. Dubensky, Drew M. Pardoll, Richard D. Schulick
Journal: Cancer Research (2006)

Improved immunization and ex vivo T-cell culture strategies can generate larger numbers and more potent tumor-specific effector cells than previously possible. Nonetheless, the capacity of these cells to eliminate established tumors is limited by their ability to efficiently enter tumor-bearing organs and mediate their effector function. In the current study, we show that the administration of an engineered organ-homing microbe selectively targets tumor-specific immune responses to metastases within that organ. Specifically, an attenuated Listeria monocytogenes strain, which preferentially infects the liver following systemic administration, dramatically enhances the activity of a cancer vaccine against liver metastases but not metastases in the lung. This enhanced activity results from both local recruitment of innate immune effectors as well as concentration and increased activation of vaccine-induced antitumor T cells within the liver. These findings show a general approach to focus systemic cancer immunotherapies to specific organs bearing tumor metastases by taking advantage of differential tropisms and the proinflammatory nature of microbes.
Physical Activity and Metabolic Risk in Individuals With a Family History of Type 2 Diabetes
Authors: Ulf Ekelund, Simon J. Griffin, Nicholas J. Wareham
Journal: Diabetes Care (2007)

We sought to examine the independent associations between different dimensions of physical activity with intermediary and clustered metabolic risk factors in overweight individuals with an increased risk of type 2 diabetes to inform future preventive action.We measured total body movement and five other subcomponents of physical activity by accelerometry in 258 adults (aged 30-50 years) with a family history of type 2 diabetes. We estimated aerobic fitness from an incremental treadmill exercise test. We measured body composition by bioimpedance and waist circumference, blood pressure, fasting triglycerides, HDL cholesterol, glucose, and insulin with standard methods. We constructed a standardized continuously distributed variable for clustered risk.Total body movement (counts . day(-1)) was significantly and independently associated with three of six risk factors (fasting triglycerides, insulin, and HDL) and with clustered metabolic risk (P = 0.004) after adjustment for age, sex, and obesity. Time spent at moderate- and vigorous-intensity physical activity (MPVA) was independently associated with clustered metabolic risk (P = 0.03). Five- and 10-min bouts of MVPA, time spent sedentary, time spent at light-intensity activity, and aerobic fitness were not significantly related with clustered risk after adjustment for confounding factors.Total body movement is associated with intermediary phenotypic risk factors for cardiovascular disease and metabolic disease and with clustered metabolic risk independent of aerobic fitness and obesity. Increasing the total amount of physical activity in sedentary and overweight individuals may have beneficial effects on metabolic risk factors.
Nitrite Infusion in Humans and Nonhuman Primates
Authors: André Dejam, Christian J. Hunter, Carole Tremonti, Ryszard M. Pluta, Yuen Yi Hon, George Grimes, Kristine Partovi, Mildred M. Pelletier, Edward H. Oldfield, Richard O. Cannon, Alan N. Schechter, Mark T. Gladwin
Journal: Circulation (2007)

The recent discovery that nitrite is an intrinsic vasodilator and signaling molecule at near-physiological concentrations has raised the possibility that nitrite contributes to hypoxic vasodilation and to the bioactivity of nitroglycerin and mediates the cardiovascular protective effects of nitrate in the Mediterranean diet. However, important questions of potency, kinetics, mechanism of action, and possible induction of tolerance remain unanswered.In the present study, we performed biochemical, physiological, and pharmacological studies using nitrite infusion protocols in 20 normal human volunteers and in nonhuman primates to answer these questions, and we specifically tested 3 proposed mechanisms of bioactivation: reduction to nitric oxide by xanthine oxidoreductase, nonenzymatic disproportionation, and reduction by deoxyhemoglobin. We found that (1) nitrite is a relatively potent and fast vasodilator at near-physiological concentrations; (2) nitrite functions as an endocrine reservoir of nitric oxide, producing remote vasodilation during first-pass perfusion of the opposite limb; (3) nitrite is reduced to nitric oxide by intravascular reactions with hemoglobin and with intravascular reductants (ie, ascorbate); (4) inhibition of xanthine oxidoreductase with oxypurinol does not inhibit nitrite-dependent vasodilation but potentiates it; and (5) nitrite does not induce tolerance as observed with the organic nitrates.We propose that nitrite functions as a physiological regulator of vascular function and endocrine nitric oxide homeostasis and suggest that it is an active metabolite of the organic nitrates that can be used therapeutically to bypass enzymatic tolerance.
GDNF rescues hyperglycemia-induced diabetic enteric neuropathy through activation of the PI3K/Akt pathway
Authors: M. Anitha
Journal: Journal of Clinical Investigation (2006)

Diabetes can result in loss of enteric neurons and subsequent gastrointestinal complications. The mechanism of enteric neuronal loss in diabetes is not known. We examined the effects of hyperglycemia on enteric neuronal survival and the effects of glial cell line–derived neurotrophic factor (GDNF) on modulating this survival. Exposure of primary enteric neurons to 20 mM glucose (hyperglycemia) for 24 hours resulted in a significant increase in apoptosis compared with 5 mM glucose (normoglycemia). Exposure to 20 mM glucose resulted in decreased Akt phosphorylation and enhanced nuclear translocation of forkhead box O3a (FOXO3a). Treatment of enteric neurons with GDNF ameliorated these changes. In streptozotocin-induced diabetic mice, there was evidence of myenteric neuronal apoptosis and reduced Akt phosphorylation. Diabetic mice had loss of NADPH diaphorase–stained myenteric neurons, delayed gastric emptying, and increased intestinal transit time. The pathophysiological effects of hyperglycemia (apoptosis, reduced Akt phosphorylation, loss of inhibitory neurons, motility changes) were reversed in diabetic glial fibrillary acidic protein–GDNF (GFAP-GDNF) Tg mice. In conclusion, we demonstrate that hyperglycemia induces neuronal loss through a reduction in Akt-mediated survival signaling and that these effects are reversed by GDNF. GDNF may be a potential therapeutic target for the gastrointestinal motility disorders related to diabetes.
FURTHER OBSERVATIONS ON THE USE OF TRIDIONE IN THE CONTROL OF PSYCHOMOTOR ATTACKS
Authors: RUSSELL N. DEJONG
Journal: American Journal of Psychiatry (1946)

Tridione, a new addition to the treatment of the cerebral dysrhythmias, is helpful in the control of psychomotor seizures. While effective in certain instances if used alone, it is most helpful if used in combination with sodium diphenylhydantoinate and/or phenobarbital. Toxic symptoms are infrequent in patients who respond to the drug, and do not constitute an important contraindication to its use. Further research on the oxazolidine-2,-4-dione derivatives and related drugs may afford further advances in the therapy of epilepsy.
Waiting times fall in Scotland, but watchdog urges caution
Authors: Bryan Christie
Journal: BMJ (2006)

The Scottish health service has been warned that it faces major challenges in meeting targets to reduce inpatients' and outpatients' waiting times.

A report from the public spending watchdog Audit Scotland says that NHS Scotland has made major progress in meeting current targets on waiting times. The number of patients waiting more than six months for inpatient or day case treatment fell by 89% between March 2001 and September 2005. The number of outpatients waiting more than six months in the same period fell by 78%.

As in England, patients in Scotland should be …
Effect of Rapamycin Alone and in Combination with Antiangiogenesis Therapy in an Orthotopic Model of Human Pancreatic Cancer
Authors: Susann Stephan, Kaustubh Datta, Enfeng Wang, Jinping Li, Rolf A. Brekken, Sareh Parangi, Philip E. Thorpe, Debabrata Mukhopadhyay
Journal: Clinical Cancer Research (2004)

The overall 5-year survival of patients with pancreatic cancer remains <5%. Novel therapeutic strategies are needed. We examined the effect of rapamycin, alone and in combination with antiangiogenesis therapy, on pancreatic cancer in vivo.
Role of blood cells in ischaemia-reperfusion induced endothelial barrier failure
Authors: S. F. Rodrigues, D. N. Granger
Journal: Cardiovascular Research (2010)

Ischaemia and reperfusion (I/R) elicits an acute inflammatory response that is characterized by the recruitment of inflammatory cells, oxidative stress, and endothelial barrier failure. Over the past three decades, much progress has been made in our understanding of the mechanisms that underlie the inflammatory response and microvascular dysfunction associated with I/R. This review is focused on the role of leucocytes (neutrophils and T-lymphocytes) and platelets, and their activation products, as mediators of I/R-induced endothelial barrier failure. The contributions of cytokines, chemokines, and oxidative stress to I/R-induced barrier dysfunction are also discussed. It concludes with an analysis of how risk factors for cardiovascular disease, i.e. hypertension, diabetes, hypercholesterolaemia, and obesity, influence the vascular permeability response to I/R. Areas of uncertainty and controversy in this field of investigation are also identified.
First Morning Voids Are More Reliable Than Spot Urine Samples to Assess Microalbuminuria
Authors: Elsbeth C. Witte, Hiddo J. Lambers Heerspink, Dick de Zeeuw, Stephan J.L. Bakker, Paul E. de Jong, Ronald Gansevoort
Journal: Journal of the American Society of Nephrology (2008)

Measurement of urinary albumin excretion (UAE) in a 24-h collection is the gold standard method to determine the presence of microalbuminuria. We sought to compare more practical alternatives—measurement of urinary albumin concentration (UAC) or albumin:creatinine ratio (ACR)—in a first morning void or in a spot urine sample with this gold standard. We asked 241 participants of a prospective cohort study to make three 24-h urine collections, a first morning void, and a spot urine sample. Regression analysis showed that the ACR in a first morning void best agreed with 24-h UAE. The prevalence of microalbuminuria determined by data from a first morning void (7.5%, whether by UAC or ACR) nearly equaled the prevalence of microalbuminuria determined by 24-h UAE (10.0%), whereas the prevalence was higher when determined by spot urine samples (25.4% for UAC and 22.4% for ACR; both P < 0.001 versus 24-h UAE). The intraindividual coefficients of variation of the ACR in a first morning void and 24-h UAE were similar (19%). Intraindividual coefficients of variations of all other measurements of albuminuria were significantly greater. In conclusion, measurement of albuminuria in a first morning void, preferably as the ACR, is more reliable than a spot urine sample to diagnose and monitor microalbuminuria.
A Low-Molecular-Weight Heparinoid Compared with Unfractionated Heparin in the Prevention of Deep Vein Thrombosis in Patients with Acute Ischemic Stroke
Authors: Alexander G.G. Turpie, Michael Gent, Robert Côte, Mark N. Levine, Jeffrey S. Ginsberg, Peter J. Powers, Jacques Leclerc, William Geerts, Richard Jay, Jean Neemeh, Marian Klimek, Jack Hirsh
Journal: Annals of Internal Medicine (1992)

▪ Objective: To compare the relative safety and efficacy of a low-molecular-weight heparinoid (ORG 10172) with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke. ▪ Design: Double-blind randomized trial. ▪ Setting: Seven Canadian university-affiliated hospitals. ▪ Participants: Eighty-seven patients with acute ischemic stroke resulting in lower-limb paresis. ▪ Intervention: Patients received either low-molecular-weight heparinoid, 750 anti-factor Xa units twice daily, or unfractionated heparin, 5000 units subcutaneously twice daily. Treatment was continued for 14 days or until hospital discharge if sooner. ▪ Measurements: Deep vein thrombosis was diagnosed using 125I-labeled fibrinogen leg scanning and impedance plethysmography. Venography was indicated if either test was positive. Overt hemorrhage, major or minor, was assessed clinically. ▪ Results: Venous thrombosis occurred in four patients (9%) given low-molecular-weight heparinoid and in 13 patients (31%) given heparin (relative risk reduction, 71%; 95% Cl, 16% to 93%. The corresponding rates for proximal vein thrombosis were 4% and 12%, respectively (relative risk reduction, 63%; P > 0.2). The incidence of hemorrhage was 2% in both groups. ▪ Conclusion: Low-molecular-weight heparinoid, given in a fixed dose of 750 anti-factor Xa units subcutaneously twice daily, is more effective than subcutaneous low-dose heparin for the prevention of deep vein thrombosis in patients with acute ischemic stroke.
THE ROLE OF COMEDONES IN ACNE VULGARIS.
Authors: M. A. Smith
Journal: British Journal of Dermatology (1962)

Journal Article THE ROLE OF COMEDONES IN ACNE VULGARIS. Get access M. A. Smith M. A. Smith Department of Dermatology, St. Bartholomew's Hospital, London, E.C.I Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 74, Issue 8-9, 1 August 1962, Pages 337–338, https://doi.org/10.1111/j.1365-2133.1962.tb13522.x Published: 01 August 1962
Increased Tubular Proliferation as an Adaptive Response to Glomerular Albuminuria
Authors: Jian-Kan Guo, Arnaud Marlier, Hongmei Shi, Alan Shan, Thomas A. Ardito, Zhao-Peng Du, Michael Kashgarian, Diane S. Krause, Daniel Biemesderfer, Lloyd G. Cantley
Journal: Journal of the American Society of Nephrology (2011)

Renal tubular atrophy accompanies many proteinuric renal diseases, suggesting that glomerular proteinuria injures the tubules. However, local or systemic inflammation and filtration of abnormal proteins known to directly injure tubules are also present in many of these diseases and animal models; therefore, whether glomerular proteinuria directly causes tubular injury is unknown. Here, we examined the renal response to proteinuria induced by selective podocyte loss. We generated mice that express the diphtheria toxin receptor exclusively in podocytes, allowing reproducible dose-dependent, specific ablation of podocytes by administering diphtheria toxin. Ablation of <20% of podocytes resulted in profound albuminuria that resolved over 1-2 weeks after the re-establishment of normal podocyte morphology. Immediately after the onset of albuminuria, proximal tubule cells underwent a transient burst of proliferation without evidence of tubular damage or increased apoptosis, resulting in an increase in total tubular cell numbers. The proliferative response coincided with detection of the growth factor Gas6 in the urine and phosphorylation of the Gas6 receptor Axl in the apical membrane of renal tubular cells. In contrast, ablation of >40% of podocytes led to progressive glomerulosclerosis, profound tubular injury, and renal failure. These data suggest that glomerular proteinuria in the absence of severe structural glomerular injury activates tubular proliferation, potentially as an adaptive response to minimize the loss of filtered proteins.
Exacerbation of respiratory symptoms in COPD patients may not be exacerbations of COPD
Authors: Bianca Beghé, Alessia Verduri, Mihai Roca, Leonardo M. Fabbri
Journal: European Respiratory Journal (2013)

To the Editor: 

Exacerbations of chronic obstructive pulmonary disease (COPD) are defined as acute events characterised by a worsening of the patient's respiratory symptoms, particularly dyspnoea, beyond day-to-day variation, leading to a change in medical treatment and/or hospitalisation [1, 2]. Exacerbations of COPD are a leading cause of hospitalisation and healthcare expenditures, particularly in frail, elderly patients. They alter the health-related quality of life and the natural course of disease, increasing the risk of mortality, both during and after the acute event [1, 2]. Patients with COPD frequently have chronic comorbidities [1]. Several of these comorbidities may produce acute events, contributing to the increased morbidity and mortality in COPD exacerbations: acute myocardial infarction, congestive heart failure, cerebrovascular disease, cardiac arrhythmias and pulmonary circulation disorders [1].

By definition, acute exacerbations of COPD are considered respiratory diseases, with specific reference to the respiratory symptoms and to the organs involved (airways and lung). Indeed, respiratory viral or bacterial infections and air pollution are assumed to be the main causes of COPD exacerbations, but the exact contribution of infections is difficult to establish, and the aetiology of a large proportion of exacerbations remains undetermined [1, 3, 4].

Although it is known that bronchoconstriction and hyperinflation contribute to the increase in dyspnoea in COPD patients, the chronic airway, pulmonary and systemic inflammation present in patients with stable COPD is associated with an acute …