tbuckley/cabot-search huggingface dataset:
Systemic levels of IL-23 are strongly associated with disease activity in rheumatoid arthritis but not spondyloarthritis
Authors: Lode Melis, Bernard Vandooren, Elli Kruithof, Peggy Jacques, Martine De Vos, Herman Mielants, Gust Verbruggen, Filip De Keyser, Dirk Elewaut
Journal: Annals of the Rheumatic Diseases (2009)

Objectives Th17 cells are an effector T-cell population that plays a role in chronic inflammatory conditions and is dependent on IL-23 for their survival and expansion. More recently, a genetic association was discovered between polymorphisms in the gene coding for the IL-23 receptor and spondyloarthritis. This study aimed to evaluate the role of Th17-associated cytokines in spondyloarthritis pathogenesis by measuring their levels in the joints and circulation as well as correlating them with disease activity parameters. Methods Paired synovial fluid (SF), serum and synovial biopsies were obtained from 30 non-PsA (psoriatic arthritis) spondyloarthritis, 22 PsA and 22 rheumatoid arthritis (RA) patients. IL-17, IL-23 and CCL20 were measured by ELISA in the SF and serum of patients and correlated with systemic and local parameters of disease activity. Results Concentrations of CCL20, a major Th17-attracting chemokine, tended to be higher in the joints of RA than in spondyloarthritis patients. Interestingly, levels of CCL20 were markedly higher in SF as opposed to serum. In addition, there was a remarkable association between the expression of the Th17 cytokine system and the presence of intimal lining layer hyperplasia in RA. Also in the serum, there was a tendency for higher IL-23 levels in RA, which correlated strongly with disease activity parameters. Conclusions Th17-related cytokines are expressed in joints of spondyloarthritis as well as RA patients. IL-23 levels, however, correlate with disease activity parameters in RA only. These results point towards a differential regulation of the Th17 cytokine system in spondyloarthritis compared with RA.
Metabolic studies of isolated human eccrine sweat glands
Authors: S. Wolfe, G. Cage, M. Epstein, L. Tice, H. Miller, R. S. Gordon
Journal: Journal of Clinical Investigation (1970)

This paper describes a method for isolating and studying the metabolism of human eccrine sweat glands. (a) Electron microscopy of glands which had been isolated and then incubated for an hour revealed no apparent alteration in morphology. (b) Known variation in gland size (male > female > children) was reflected in the relative rates of lactate production. (c) Lactate production was approximately 1.5 nmoles/gland per hr in the absence of glucose and rose to 2.7 at physiological concentrations of glucose (5.6 mmoles/liter). This amount of lactate production agrees well with the amounts found in sweat. (d) Both adrenergic (epinephrine) and cholinergic (methacholine) stimuli increased lactate production. (e) Glycogen depletion was demonstrated during incubation. (f) O(2) consumption was measured and aerobic metabolism was found to account for less than 1% of the energy derived from anaerobic pathways. These studies demonstrate that the large amounts of lactate appearing in human eccrine sweat can be accounted for by glandular metabolism and that both glycogen and glucose can be used as substrates.
Two months of endurance training does not alter diastolic function evaluated by TDI in 9–11-year-old boys and girls
Authors: P Obert, S Nottin, G Baquet, D Thevenet, F-X Gamelin, S Berthoin
Journal: British Journal of Sports Medicine (2007)

Superior global cardiac performance (ie stroke volume) is classically reported after training in children. Current knowledge of the impact of exercise training on myocardial relaxation, a major component of left ventricular (LV) filling and subsequently stroke volume, is, however, limited in the paediatric population. This study aimed to investigate the effect of aerobic training on LV wall motion velocities by tissue Doppler imaging (TDI) in healthy children.25 children (11 girls, 14 boys) were enrolled in a 2 month high-intensity aerobic training programme and 25 (12 girls and 13 boys) served as controls. The children (9-11 years old) performed a graded maximal exercise test on a treadmill to evaluate maximal oxygen uptake. Standard Doppler echocardiography and TDI measurements were performed at baseline and end of the study. Tissue Doppler systolic, early and late myocardial velocities were obtained at the mitral annulus in the septal, lateral, inferior and posterior walls.Maximal oxygen uptake increased by 6.5% (before: 51.6 (SD 4.2), after: 55.0 (4.5) ml/min/kg p<0.001) after training. A modest but significant increase in left ventricular end-diastolic diameter was also noticed (before: 46.1 (3.4), after: 48.3 (4.3) mm.BSA(-1/2), p<0.001), whereas left ventricular wall thickness and mass were unchanged. Neither transmitral inflow velocities nor early and late wall motion (Em: before = 18.4 (2.7), after = 18.0 (2.3) cm/s, Am: before = 6.8 (1.2), after = 6.7 (1.3) cm/s) were affected by training. Shortening fraction and regional systolic function (Sm: before = 10.1 (1.6), after = 10.2 (1.4) cm/s) by TDI were also unchanged.High-intensity aerobic sessions repeated over a 2 month period failed to improve regional diastolic function assessed by TDI in healthy young children.
Predictors of residual sleepiness in adequately treated obstructive sleep apnoea patients
Authors: I. Koutsourelakis, E. Perraki, N. T. Economou, P. Dimitrokalli, E. Vagiakis, C. Roussos, S. Zakynthinos
Journal: European Respiratory Journal (2009)

Some patients with obstructive sleep apnoea syndrome (OSAS; respiratory distress index (RDI) of >5 events.h(-1)) experience residual excessive daytime subjective sleepiness (Epworth Sleepiness Scale (ESS) score of >10), despite adequate use of continuous positive airway pressure (CPAP) therapy. The aim of the present study was to identify clinical and polysomnographic predictors of this sleepiness. Clinical and polysomnographic variables and ESS score were evaluated in 208 OSAS patients with an ESS score of >10 before (initial assessment) and after > or =6 months of adequate (> or =4 h.day(-1)) CPAP use. Following CPAP treatment, 114 (55%) patients showed an abnormal ESS score (>10; CPAP nonresponders), whereas 94 (45%) showed a normal ESS score (<11; CPAP responders). Of the CPAP responders, none had a history of depression, whereas the converse was true for 38.8% of CPAP nonresponders. In addition, multivariate logistic regression analysis revealed that the independent predictors of residual excessive daytime sleepiness following CPAP therapy were a history of diabetes and heart disease, and a higher ESS score and lower RDI on initial assessment. In conclusion, predictors of residual excessive sleepiness in adequately CPAP-treated OSAS were a history of depression, diabetes and heart disease, and a higher ESS score and lower RDI on initial assessment.
Total and High-Molecular-Weight Adiponectin and Risk of Incident Diabetes in Older People
Authors: Jorge R. Kizer, Alice M. Arnold, David Benkeser, Joachim H. Ix, Luc Djousse, Susan J. Zieman, Joshua I. Barzilay, Russell P. Tracy, Christos S. Mantzoros, David S. Siscovick, Kenneth J. Mukamal
Journal: Diabetes Care (2011)

To delineate the associations of total adiponectin, high-molecular-weight (HMW) adiponectin, and the HMW-to-total adiponectin ratio with diabetes in older adults.Total and HMW adiponectin were measured in a population-based study of older adults. The relations of total adiponectin, HMW adiponectin, and their ratio with incident diabetes (n = 309) were assessed in 3,802 individuals.Total and HMW adiponectin were highly correlated (r = 0.94). Analysis using cubic splines revealed that the associations between total and HMW adiponectin and new-onset diabetes were not linear. Specifically, after adjustment for confounders, there were similar inverse relationships for total (hazard ratio per SD 0.49 [95% CI 0.39-0.63]) and HMW adiponectin (0.42 [0.32-0.56]) with diabetes up to values of 20 and 10 mg/L, respectively, above which the associations plateaued. These associations persisted after adjustment for potential mediators (blood pressure, lipids, C-reactive protein, and homeostasis model assessment of insulin resistance [HOMA-IR]). There was, however, evidence of interaction by HOMA-IR in the lower range of adiponectin, with stronger inverse associations among insulin-sensitive than insulin-resistant participants. HMW-to-total adiponectin ratio showed a linear adjusted association with outcome, but this was abolished by inclusion of mediating variables.In this older cohort, increasing concentrations of total and HMW adiponectin were associated with comparably lower risks of diabetes, but these associations leveled off with further increases above concentrations of 20 and 10 mg/L, respectively. The more pronounced risk decreases at the lower range among participants without insulin resistance support a role for adiponectin that is independent of baseline hyperinsulinemia, but this will require further investigation.
Characteristics of COPD exacerbations in Greece
Authors: Foteini Malli, Zoe Daniil, Eleni Bania, Evangelos C. Alexopoulos, Nikolaos Tzanakis, Epaminondas Kosmas, Michael Toumbis, Konstantinos I. Goyrgoulianis
Journal: European Respiratory Journal (2012)

Background and Aims : Acute Exacerbations of COPD (AECOPD) are associated with significant morbidity and mortality. We aimed to provide data on the characteristics of AECOPD in a large group of COPD patients in Greece.

Methods: Patients diagnosed with an AECOPD referred to 27 Greek hospitals and 114 chest specialists were included. Demographic data, previous treatment, lung function testing and co-morbidity were recorded.

Results : Six thousand and fourteen patients were included in the study, 4360 (72.5%) males, age median (interquartile): 68(60-75) yrs. Up to 47.8% of patients were current smokers. Median BMI was 27.5kg/m2 (24.9-30.6). Two or more co morbidities were found in 55.8%. The vast majority of the patients (86.4%) were receiving regular treatment for COPD before the exacerbation. The majority of patients (61%) were classified as moderate-to-severe COPD. Almost ¼ (23.4%) of patients had hypoxemic respiratory failure and 10.3% of them developed hypercapnia during stable state. A remarkable percentage of patients (28.3%) experienced more than 3 exacerbations. Patients aged >76 yrs had increased number of AECOPD vs patients aged 5 yrs, COPD stages of 3 or 4, comorbidity and non compliance with treatment were associated with increased annual frequency of AECOPD. Increased disease duration (>11 yrs), COPD stage 4 and non compliant patients demonstrated increased OR for ICU admission (OR(95%CI): 1.8 (1.1-2.81), p=0.018, 2.8 (1.4-5.5), p=0.002, 1.4 (1.0-2.0), p=0.043, respectively).

Conclusions: Our study showed that patients presenting AECOPD have a wide range of severity, while the exacerbation rate is associated with age, disease severity stage, comorbidity and compliance with regular treatment.
Spatially Oriented, Temporally Sequential Smooth Muscle Cell-Endothelial Progenitor Cell Bi-Level Cell Sheet Neovascularizes Ischemic Myocardium
Authors: Yasuhiro Shudo, Jeffrey E. Cohen, John W. MacArthur, Pavan Atluri, Philip F. Hsiao, Elaine C. Yang, Alexander S. Fairman, Alen Trubelja, Jay Patel, Shigeru Miyagawa, Yoshiki Sawa, Y. Joseph Woo
Journal: Circulation (2013)

Background— Endothelial progenitor cells (EPCs) possess robust therapeutic angiogenic potential, yet may be limited in the capacity to develop into fully mature vasculature. This problem might be exacerbated by the absence of a neovascular foundation, namely pericytes, with simple EPC injection. We hypothesized that coculturing EPCs with smooth muscle cells (SMCs), components of the surrounding vascular wall, in a cell sheet will mimic the native spatial orientation and interaction between EPCs and SMCs to create a supratherapeutic angiogenic construct in a model of ischemic cardiomyopathy. Methods and Results— Primary EPCs and SMCs were isolated from Wistar rats. Confluent SMCs topped with confluent EPCs were spontaneously detached from the Upcell dish to create an SMC-EPC bi-level cell sheet. A rodent ischemic cardiomyopathy model was created by ligating the left anterior descending coronary artery. Rats were then immediately divided into 3 groups: cell-sheet transplantation (n=14), cell injection (n=12), and no treatment (n=13). Cocultured EPCs and SMCs stimulated an abundant release of multiple cytokines in vitro. Increased capillary density and improved blood perfusion in the borderzone elucidated the significant in vivo angiogenic potential of this technology. Most interestingly, however, cell fate–tracking experiments demonstrated that the cell-sheet EPCs and SMCs directly migrated into the myocardium and differentiated into elements of newly formed functional vasculature. The robust angiogenic effect of this cell sheet translated to enhanced ventricular function as demonstrated by echocardiography. Conclusions— Spatially arranged EPC-SMC bi-level cell-sheet technology facilitated the natural interaction between EPCs and SMCs, thereby creating structurally mature, functional microvasculature in a rodent ischemic cardiomyopathy model, leading to improved myocardial function.
Human Antitetanus Serum in the Treatment of Tetanus
Authors: M. Ellis
Journal: BMJ (1963)

MEDICAL JOURNAL trophins, and two days after the last injection a laparotomy was performed.The ovaries were unchanged in size; the cysts were punctured and the fluid was collected for examina- tion, and bilateral wedge resections were then performed.Case 4A single woman aged 27 started to menstruate at the age of 14.She was regular for the first year and then had only one or two periods yearly until she was 21, when she was treated with stilboestrol.Since then she has had scanty irregular periods lasting two to four days at intervals of one to four months.She first noticed the growth of hair on her lips and chin at the age of 16.It became coarse and spread on to her breasts, abdominal wall, and legs.She complained of headache, pain in the limbs, and depression, for which she was treated by a psychiatrist.Her weight was constant.She was admitted and examined under anaesthesia, and her pelvis appeared to be normal.Culdoscopy was unsatis- factory.The left ovary was poorly visualized and its size could not be estimated.The left Fallopian tube was red and deformed.There was a tubovarian mass in the right
Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy
Authors: Linda F. Fried, Nicholas Emanuele, Jane H. Zhang, Mary Brophy, Todd A. Conner, William Duckworth, David J. Leehey, Peter A. McCullough, Theresa O'Connor, Paul M. Palevsky, Robert F. Reilly, Stephen L. Seliger, Stuart R. Warren, Suzanne Watnick, Peter Peduzzi, Peter Guarino
Journal: New England Journal of Medicine (2013)

Combination therapy with angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) decreases proteinuria; however, its safety and effect on the progression of kidney disease are uncertain. Methods We provided losartan (at a dose of 100 mg per day) to patients with type 2 diabetes, a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 300, and an estimated glomerular filtration rate (GFR) of 30.0 to 89.9 ml per minute per 1.73 m(2) of body-surface area and then randomly assigned them to receive lisinopril (at a dose of 10 to 40 mg per day) or placebo. The primary end point was the first occurrence of a change in the estimated GFR (a decline of ≥ 30 ml per minute per 1.73 m(2) if the initial estimated GFR was ≥ 60 ml per minute per 1.73 m(2) or a decline of ≥ 50% if the initial estimated GFR was <60 ml per minute per 1.73 m(2)), end-stage renal disease (ESRD), or death. The secondary renal end point was the first occurrence of a decline in the estimated GFR or ESRD. Safety outcomes included mortality, hyperkalemia, and acute kidney injury. Results The study was stopped early owing to safety concerns. Among 1448 randomly assigned patients with a median follow-up of 2.2 years, there were 152 primary end-point events in the monotherapy group and 132 in the combination-therapy group (hazard ratio with combination therapy, 0.88; 95% confidence interval [CI], 0.70 to 1.12; P=0.30). A trend toward a benefit from combination therapy with respect to the secondary end point (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P=0.10) decreased with time (P=0.02 for nonproportionality). There was no benefit with respect to mortality (hazard ratio for death, 1.04; 95% CI, 0.73 to 1.49; P=0.75) or cardiovascular events. Combination therapy increased the risk of hyperkalemia (6.3 events per 100 person-years, vs. 2.6 events per 100 person-years with monotherapy; P<0.001) and acute kidney injury (12.2 vs. 6.7 events per 100 person-years, P<0.001). Conclusions Combination therapy with an ACE inhibitor and an ARB was associated with an increased risk of adverse events among patients with diabetic nephropathy. (Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; VA NEPHRON-D ClinicalTrials.gov number, NCT00555217.).
The International Classification of Functioning, Disability and Health (ICF) Core Sets for rheumatoid arthritis: a way to specify functioning
Authors: G Stucki
Journal: Annals of the Rheumatic Diseases (2004)

Today, patients' functioning is a central issue in medicine. Concepts, classifications, and measurements of functioning and health, such as the International Classification of Functioning, Disability and Health (ICF) are of prime importance in clinical practice, teaching, and research. This report compares the contents of three of the most widely used health status measures in rheumatoid arthritis (RA), namely the Health Assessment Questionnaire disability index (HAQ), the Arthritis Impact Measurement Scales 2 (AIMS2), and the Short Form health survey (SF-36) based on the ICF. In addition, their content is compared to the Comprehensive ICF Core Set for RA. The comparisons illustrate that the different health status measures cover different components, and that they cover the different components with different level of precision. Using the ICF as a reference framework allows a researcher or a recommending instance to see which domains are covered in a specific instrument and, therefore, whether it is necessary to complement the study with other measures. Nevertheless, which specific health status measures to recommend still remains a challenge. If enough care is taken to define "what should be measured", it could form the basis for a solid and stable recommendation, adhered to for many years.
Getting a Grip on Aromatase Inhibitor–Associated Arthralgias
Authors: Dawn L. Hershman
Journal: Journal of Clinical Oncology (2008)

reported large variability in reports of musculoskeletal disorders, with rates of patients on AIs ranging from 5% to 35%. In the community, the rate of AI-related arthralgia appears to be higher. In a survey of 200 patients with breast cancer on adjuvant AI therapy, more than 40% of women reported worsening or new-onset joint pain or stiffness after starting AIs. 9 Among those with AI-related joint symptoms, about two thirds experienced moderate to severe symptoms. This variability reflects a critical issue with regard to clinical trial toxicity assessments and patient reported symptoms.
Role of Ischemia and of Hypoxia-Inducible Genes in Arteriogenesis After Femoral Artery Occlusion in the Rabbit
Authors: Elisabeth Deindl, Ivo Buschmann, Imo E. Hoefer, Thomas Podzuweit, Kerstin Boengler, Sabina Vogel, Niels van Royen, Borja Fernandez, Wolfgang Schaper
Journal: Circulation Research (2001)

Vascular endothelial growth factor (VEGF) is known to play an important role in angiogenesis. Its place in collateral artery growth (arteriogenesis), however, is still debated. In the present study, we analyzed the expression of VEGF and its receptors (Flk-1 and Flt-1) in a rabbit model of collateral artery growth after femoral artery occlusion. Hypoxia presents the most important stimulus for VEGF expression. We therefore also investigated the expression level of distinct hypoxia-inducible genes (HIF-1alpha, LDH A) and determined metabolic intermediates indicative for ischemia (ATP, creatine phosphate, and their catabolites). We found that arteriogenesis was not associated with an increased expression of VEGF or the mentioned hypoxia-inducible genes. Furthermore, the high-energy phosphates and their catabolites were entirely within normal limits. Despite the absence of an increased expression of VEGF and its receptors, collateral vessels increased their diameter by a factor of 10. The speed of collateral development could be increased by infusion of the chemoattractant monocyte chemotactic protein-1 but not by infusion of a 30 times higher concentration of VEGF. From these data, we conclude that under nonischemic conditions, arteriogenesis is neither associated with nor inducible by increased levels of VEGF and that VEGF is not a natural agent to induce arteriogenesis in vivo.
Redox-active Protein Thioredoxin Prevents Proinflammatory Cytokine- or Bleomycin-induced Lung Injury
Authors: Tomoaki Hoshino, Hajime Nakamura, Masaki Okamoto, Seiya Kato, Shinichi Araya, Keiko Nomiyama, Kotaro Oizumi, Howard A. Young, Hisamichi Aizawa, Junji Yodoi
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Thioredoxin (TRX) is a multifunctional redox (reduction/oxidation)-active protein that scavenges reactive oxygen species by itself or together with TRX-dependent peroxiredoxin. TRX also has chemotaxis-modulating functions and suppresses leukocyte infiltration into sites of inflammation. Leukocyte infiltration and oxidative stress may be involved in the pathogenesis of several diseases, including interstitial lung diseases (ILD). We examined the effects of TRX in two mouse models of human ILD. Recently, we established a new mouse model for human ILD in which daily administration of proinflammatory cytokine interleukin (IL)-18 with IL-2 induces lethal lung injury accompanied by acute interstitial inflammatory responses. Administration of recombinant TRX suppressed IL-18/IL-2-induced interstitial infiltration of cells and prevented death and lung tissue damage. TRX-transgenic mice also showed resistance to lethal lung injury caused by IL-18/IL-2. Administration of bleomycin induces the infiltration of polymorphonuclear and mononuclear leukocytes in the pulmonary interstitium, followed by progressive fibrosis. Wild-type mice given recombinant TRX treatment and TRX-transgenic mice demonstrated a decrease in bleomycin-induced cellular infiltrates and fibrotic changes in the lung tissue. These results suggest that TRX modulates pulmonary inflammatory responses and acts to prevent lung injury. TRX may have clinical benefits in human ILD, including lung fibrosis, for which no effective therapeutic strategy currently exists.
COMPARISON OF INFLAMMATORY MARKERS FOR PREDICTION OF NEOINTIMAL HYPERPLASIA PROLIFERATION AFTER DRUG-ELUTING STENT IMPLANTATION
Authors: Woong Chol Kang, Yae Min Park, Chan IL Moon, Kyounghoon Lee, Kwen-Chul Shin, Myeong Gun Kim, Kyong Yong Oh, Eui Joo Kim, Seung Hwan Han, Taehoon Ahn, Eak Kyun Shin
Journal: Journal of the American College of Cardiology (2011)