tbuckley/cabot-search huggingface dataset:
Osteophytes and joint space narrowing are independently associated with pain in finger joints in hand osteoarthritis
Authors: Marion C Kortekaas, Wing-Yee Kwok, Monique Reijnierse, Tom W J Huizinga, Margreet Kloppenburg
Journal: Annals of the Rheumatic Diseases (2011)

Objective To study the associations between structural abnormalities on ultrasound (US) or conventional x-rays (CR) and pain in hand osteoarthritis (HOA). Methods In 55 consecutive patients with HOA (mean age 61 years, 86% women) fulfilling the American College of Rheumatology criteria, pain in 30 separate hand joints was assessed upon palpation; osteophytes were assessed by US and CR and joint space narrowing (JSN) by CR. Associations between structural abnormalities and pain per joint were analysed using generalised estimated equations to account for patient effects and adjusted for age, sex, body mass index, US inflammatory features and other remaining structural abnormalities. Results In 1649 joints, 69% and 46% had osteophytes on US and CR, respectively and 47% had JSN. Osteophytes and JSN showed independent associations with pain per joint adjusted: OR for osteophytes: 4.8 (95% CI 3.1 to 7.5) for US and 4.1 (95% CI 2.4 to 7.1) for CR; for JSN: 4.2 (95% CI 2.0 to 9.0). Conclusions Osteophytes and JSN are independently associated with pain in individual HOA joints, taking into account patient effects.
THE SIGNIFICANCE OF COLOSTRUM TO THE NEW-BORN CALF
Authors: Theobald Smith, Ralph B. Little
Journal: The Journal of Experimental Medicine (1922)

All of ten calves which were permitted to take colostrum after birth survived. Eight out of twelve calves which did not get colostrum died and one was killed moribund. One calf, killed on the 27th day, harbored miscellaneous bacteria in its organs. The kidneys were sclerotic and one joint diseased. Of the remaining two calves, one had transitory joint troubles, the other rhinitis. One was sold and the other killed when 2 months old. In the latter the organs were normal and sterile.
The anti-malarial drug halofantrine and its metabolite N-desbutylhalofantrine block HERG potassium channels
Authors: M Mbai
Journal: Cardiovascular Research (2002)

The antimalarial drug halofantrine has been associated with QT interval prolongation and with fatal and nonfatal arrhythmias in patients without known underlying cardiac abnormalities. A common target for QT interval-prolonging drugs is the human ether-a-go-go gene (HERG) which encodes the pore forming subunit of the rapidly activating delayed rectifier K(+) current (I(Kr)).We studied the effects of halofantrine (0.1-1000 nM) and its major metabolite N-desbutylhalofantrine (3-1000 nM) on wild type HERG K(+) channels stably expressed in HEK 293 cells, using the whole cell patch-clamp recording technique.Halofantrine and N-desbutylhalofantrine blocked HERG K(+) channels in a concentration-dependent manner with a half-maximal inhibitory concentration of 21.6 nM (n=31 cells) and 71.7 nM (n=18 cells), respectively. The development of drug block for both halofantrine and N-desbutylhalofantrine required channel activation indicative of open and/or inactivated state block. Drug washout or cell hyperpolarization resulted in minimal current recovery consistent with virtually irreversible binding. Using a ventricular action potential voltage clamp protocol, halofantrine and N-desbutylhalofantrine block of HERG current was greatest during phases 2 and 3 of the action potential waveform.We conclude that both halofantrine and N-desbutylhalofantrine cause high affinity block of HERG K(+) channels. Although N-desbutylhalofantrine has been suggested to be a safer antimalarial agent compared to halofantrine, our results suggest that the gain in the safety margin for QT interval prolongation-related cardiotoxicity is minimal.
The effect of topical tacrolimus on severe recalcitrant chronic discoid lupus erythematosus
Authors: S.L. Walker, B. Kirby, R.J.G. Chalmers
Journal: British Journal of Dermatology (2002)

Journal Article The effect of topical tacrolimus on severe recalcitrant chronic discoid lupus erythematosus Get access S.L. Walker, S.L. Walker Dermatology Centre, Hope Hospital, University of Manchester Medical School, Salford M6 8HD, U.K. E‐mail: drstevewalker@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar B. Kirby, B. Kirby Dermatology Centre, Hope Hospital, University of Manchester Medical School, Salford M6 8HD, U.K. E‐mail: drstevewalker@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar R.J.G. Chalmers R.J.G. Chalmers Dermatology Centre, Hope Hospital, University of Manchester Medical School, Salford M6 8HD, U.K. E‐mail: drstevewalker@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 147, Issue 2, 1 August 2002, Page 405, https://doi.org/10.1046/j.1365-2133.2002.488616.x Published: 01 August 2002
β-Adrenergic Blockade in Developing Heart Failure
Authors: Sumanth D. Prabhu, Bysani Chandrasekar, David R. Murray, Gregory L. Freeman
Journal: Circulation (2000)

Whether beta-adrenergic blockade modulates myocardial expression of inflammatory cytokines and nitric oxide (NO) in heart failure is unclear.We administered oral metoprolol or no therapy to rats for 12 weeks after large myocardial infarction and subsequently examined left ventricular (LV) remodeling; myocardial tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 expression; and NO. In untreated rats, echocardiography revealed significant (P<0.001) LV dilatation and systolic dysfunction compared with sham. Papillary muscle studies revealed isoproterenol hyporesponsiveness to be unaltered by NO synthase (NOS) inhibition. Circulating NO metabolites were undetectable. In noninfarcted myocardium, although inducible NOS (iNOS) mRNA was absent, TNF-alpha, IL-1beta, and IL-6 mRNA and protein were markedly elevated compared with sham (P<0.001), with 2-fold higher expression (P<0.025) of IL-6 compared with TNF-alpha or IL-1beta. Metoprolol administration starting 48 hours after infarction (1) attenuated (P<0.02) LV dilatation and systolic dysfunction, (2) preserved isoproterenol responsiveness (P<0.025) via NO-independent mechanisms, and (3) reduced myocardial gene expression and protein production of TNF-alpha and IL-1beta (P<0. 025) but not IL-6, which remained high.During heart failure development, adrenergic activation contributes to increased myocardial expression of TNF-alpha and IL-1beta but not IL-6, and one mechanism underlying the beneficial effects of beta-adrenergic blockade may involve attenuation of TNF-alpha and IL-1beta expression independent of iNOS and NO.
Gender Differences in Outcomes After Hospital Discharge From Coronary Artery Bypass Grafting
Authors: Veena Guru, Stephen E. Fremes, Peter C. Austin, Eugene H. Blackstone, Jack V. Tu
Journal: Circulation (2006)

Background— There are few comparative data regarding long-term nonfatal outcomes for women versus men after coronary artery bypass grafting (CABG). This study compares gender differences in cardiac events in a population of hospital survivors up to 11 years after isolated CABG surgery in Ontario, Canada. Methods and Results— A population-based cohort study (n=68 774 patients, 15 043 women) between September 1, 1991, and April 1, 2002, was assembled with linked clinical and administrative databases. Cox modeling and propensity score matching were used to compare death, cardiac readmission (angina, heart failure, myocardial infarction), repeat revascularization (angioplasty or CABG), and stroke readmission between men and women. Women were older (65±17 versus 62±13 years), more likely to present with urgent or emergent status (64% versus 56%), and less likely to receive arterial grafts (70% versus 78%). Women had a higher rate of cardiac readmission in the first year after surgery (hazard ratio [HR] of 1.5, 95% confidence interval [CI] 1.36 to 1.56), and this increased risk persisted after 1 year (HR 1.2, 95% CI 1.14 to 1.31). This was primarily due to readmissions for unstable angina (HR 1.3, 95% CI 1.24 to 1.38) and congestive heart failure (HR 1.1, 95% CI 1.06 to 1.21). Propensity-matched women had similar rates of death (HR 0.9, 95% CI 0.83 to 0.98) and repeat revascularization (HR 1.0, 95% CI 0.91 to 1.06). Conclusions— Women have a more complex clinical preoperative presentation and are more likely to be readmitted with unstable angina and congestive heart failure after CABG but experience survival similar to those seen in men. Gender differences in outcomes may be improved through durable revascularization strategies and close postoperative follow-up care targeted to women.
Hematopoietic stem cell transplantation (HSCT) in children with juvenile myelomonocytic leukemia (JMML): results of the EWOG-MDS/EBMT trial
Authors: Franco Locatelli, Peter Nöllke, Marco Zecca, Elisabeth Korthof, Edoardo Lanino, Christina Peters, Andrea Pession, Hartmut Kabisch, Cornelio Uderzo, Carmen S. Bonfim, Peter Bader, Dagmar Dilloo, Jan Stary, Alexandra Fischer, Tom Révész, Monika Führer, Henrik Hasle, Monika Trebo, Marry M. van den Heuvel-Eibrink, Susanna Fenu, Brigitte Strahm, Giovanna Giorgiani, Mario Regazzi Bonora, Ulrich Duffner, Charlotte M. Niemeyer
Journal: Blood (2004)
Xenopus
Authors: Elizabeth A. Jones
Journal: Journal of the American Society of Nephrology (2005)

Recent advances in techniques that are available to study the molecular development of the frog <i>Xenopus</i> make developmental studies using this amphibian amenable to experimentation. This review outlines some of the attractive features of this model organism and describes how these techniques can be and are being used in studies on the organogenesis of the larval amphibian kidney, the pronephros. The roles of micromanipulation, grafting, and <i>in vitro</i> culturing of animal caps are discussed as tools in the analysis of kidney development and as a source of tissue for subtractive hybridization strategies. The importance of expression cloning and functional analysis of newly identified pronephros-specific genes are also described. Finally, transgenesis and electroporation are discussed as potentially new methods of gene delivery to the pronephros. These techniques can be used to help identify the gene networks that control organogenesis of this larval kidney form, which will undoubtedly have applicability to higher vertebrate kidney development.
Neural Crest Cells Retain Multipotential Characteristics in the Developing Valves and Label the Cardiac Conduction System
Authors: Tomoki Nakamura, Melissa C. Colbert, Jeffrey Robbins
Journal: Circulation Research (2006)

Multipotent neural crest cells (NCCs) are a major extracardiac component of cardiovascular development. Although recognized as contributing cells to the arterial valves at early developmental stages, NCC persistence in the valves at later times or in the adult heart is controversial. We analyzed NCC persistence and contributions to both semilunar and atrioventricular (AV) valves in the mature heart. Two NCC-specific promoters driving Cre recombinase, Wnt1-Cre and P0-Cre, were mated with floxed reporter mice, R26R or CAG-CAT-EGFP, to map NCC fate. Hearts were analyzed before aorticopulmonary (AP) septation through adult stages. As previously demonstrated, strong NCC labeling was detected in ventral and dorsal outflow cushions before AP septation. In contrast to previous reports, we found that substantial numbers of labeled cells persisted in the semilunar valves in late fetal, neonatal, and adult hearts. Furthermore, NCCs were also found in the AV valves, almost exclusively in the septal leaflets. NCCs in the AV valves expressed melanocytic and neurogenic markers. However, cells labeled in the proximal cardiac conduction system exhibited neurogenic and gliagenic markers, whereas some NCCs expressed no differentiation specific markers. These results suggest that cardiac NCCs contribute to the mature valves and the cardiac conduction system and retain multipotent characteristics late in development.
Thermal Enhancement with Optically Activated Gold Nanoshells Sensitizes Breast Cancer Stem Cells to Radiation Therapy
Authors: Rachel L. Atkinson, Mei Zhang, Parmeswaran Diagaradjane, Sirisha Peddibhotla, Alejandro Contreras, Susan G. Hilsenbeck, Wendy A. Woodward, Sunil Krishnan, Jenny C. Chang, Jeffrey M. Rosen
Journal: Science Translational Medicine (2010)

Local hyperthermia with gold nanoshells sensitizes cancer stem cells to radiation treatment in mouse and human breast cancer preclinical models.
Variation in the Ratio of Nucleotide Substitution and Indel Rates across Genomes in Mammals and Bacteria
Authors: J.-Q. Chen, Y. Wu, H. Yang, J. Bergelson, M. Kreitman, D. Tian
Journal: Molecular Biology and Evolution (2009)

Rates of nucleotide substitution and insertion/deletion (indel) are known to vary across the functional components of a genome. Little attention has been paid, however, to the quantitative relationship between the two. Here we investigate the ratio of nucleotide substitutions to indels (S/I) in different regions of 4 primates, 70 bacteria, and 8 other genomes. We find that the ratio differs at 5.4-times between coding and noncoding, 3.3-times between conserved and less conserved coding sequences, and 1.46-times between nonrepeat and repeat regions. The S/I ratio is also positively correlated with the level of divergence between the genomes compared. Our results suggest that the S/I ratio may reflect differences in the efficacy of selection against indels. Due to the sensitivity of indel density in different regions, this ratio varies over a much larger range. With the recent discovery suggesting that indels act as local enhancers of mutation in surrounding sequences, nucleotide substitution rates are expected to be accelerated in regions of low constraint, where indels tend to accumulate, but will otherwise be modulated in proportion to the level of a sequence's functional constraint. Indels, therefore, may play a nontrivial role in controlling differences in genetic variation and divergence across functional regions of a genome.
Methylation of <b> <i>p16</i> </b> CpG Islands Associated with Malignant Transformation of Gastric Dysplasia in a Population-Based Study
Authors: Yu Sun, Dajun Deng, Wei-Cheng You, Hua Bai, Lian Zhang, Jing Zhou, Lin Shen, Jun-Ling Ma, Yu-Quan Xie, Ji-You Li
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Inactivation of p16 by aberrant methylation of CpG islands is a frequent event in carcinomas and precancerous lesions of various organs, including the stomach. The aim of this study is to investigate the relationship between p16 methylation and malignant transformation of human gastric dysplasia (DYS) based on follow-up endoscopic screening in a high-risk population. Experimental Design: Genomic DNA samples were extracted from paraffin blocks of gastric mucosal biopsies that were histopathologically diagnosed as low-grade DYS from patients who developed gastric carcinomas [GCs (n = 21)] and those that did not do so (n = 21) during 5 years of follow-up. The methylation status of p16 CpG islands of each sample was detected by methylation-specific PCR, denatured high-performance liquid chromatography, and sequencing. Results: Aberrant p16 methylation was observed in 5 of 21 samples of DYS that progressed to GC but in 0 of 21 samples that did not progress to GC (P = 0.048, two-sided). Sequencing results confirmed that all CpG sites were methylated in the analyzed sequence from these five p16-methylated cases. Furthermore, p16 methylation was also observed in the five subsequent GCs. Unmethylated p16 CpG islands were detected in all of the samples without p16 methylation. Conclusions: Our findings suggest p16 methylation is correlated with the malignant transformation of gastric DYS, and p16 methylation might be a useful biomarker for prediction of malignant potential of gastric DYS.
Management of spontaneous pneumothorax: state of the art
Authors: J-M. Tschopp, R. Rami-Porta, M. Noppen, P. Astoul
Journal: European Respiratory Journal (2006)

Spontaneous pneumothorax remains a significant health problem. However, with time, there have been improvements in pathogenesis, diagnostic procedures and both medical and surgical approaches to treatment. Owing to better imaging techniques, it is now clear that there is almost no normal visceral pleura in the case of spontaneous pneumothorax, and that blebs and bullae are not always the cause of pneumothorax. In first episodes of primary spontaneous pneumothorax, observation and simple aspiration are established first-line therapies, as proven by randomised controlled trials. Aspiration should be better promoted in daily medical practice. In the case of recurrent or persistent pneumothorax, simple talc poudrage under thoracoscopy has been shown to be safe, cost-effective and no more painful than a conservative treatment using a chest tube. There are also new experimental data showing that talc poudrage, as used in Europe, does not lead to serious side-effects and is currently the best available pleural sclerosing agent. Alternatively, surgical techniques have considerably improved, and are now less invasive, especially due to the development of video-assisted thoracoscopic surgery. Studies suggest that video-assisted thoracoscopic surgery may be more cost-effective than chest tube drainage in spontaneous pneumothorax requiring chest tube drainage, although it is more expensive than simple thoracoscopy and requires general anaesthesia, double-lumen tube intubation and ventilation. Recommendations are made regarding the treatment of pneumothorax. In secondary or complicated primary pneumothorax, i.e. recurrent or persistent pneumothorax, some diffuse treatment of the visceral pleura should be offered, either by talc poudrage under thoracoscopy or by video-assisted thoracoscopic surgery. Moreover, all of these new techniques should be better standardised to permit comparison in randomised controlled studies.
Prognosis After Aortic Valve Replacement With a Bioprosthesis
Authors: J. P. A. Puvimanasinghe, E. W. Steyerberg, J. J. M. Takkenberg, M. J. C. Eijkemans, L. A van Herwerden, A. J. J. C. Bogers, J. D. F. Habbema
Journal: Circulation (2001)

Background —Bioprostheses are widely used as an aortic valve substitute, but knowledge about prognosis is still incomplete. The purpose of this study was to provide insight into the age-related life expectancy and actual risks of reoperation and valve-related events of patients after aortic valve replacement with a porcine bioprosthesis. Methods and Results —We conducted a meta-analysis of 9 selected reports on stented porcine bioprostheses, including 5837 patients with a total follow-up of 31 874 patient-years. The annual rates of valve thrombosis, thromboembolism, hemorrhage, and nonstructural dysfunction were 0.03%, 0.87%, 0.38%, and 0.38%, respectively. The annual rate of endocarditis was estimated at 0.68% for &gt;6 months of implantation and was 5 times as high during the first 6 months. Structural valve deterioration was described with a Weibull model that incorporated lower risks for older patients. These estimates were used to parameterize, calibrate, and validate a mathematical microsimulation model. The model was used to predict life expectancy and actual risks of reoperation and valve-related events after implantation for patients of different ages. For a 65-year-old male, these figures were 11.3 years, 28%, and 47%, respectively. Conclusions —The combination of meta-analysis with microsimulation enabled a detailed insight into the prognosis after aortic valve replacement with a bioprosthesis for patients of different ages. This information will be useful for patient counseling and clinical decision making. It also could serve as a baseline for the evaluation of newer valve types.
Beta-adrenergic receptor distribution among muscle fiber types and resistance arterioles of white, red, and intermediate skeletal muscle.
Authors: W H Martin, S S Murphree, J E Saffitz
Journal: Circulation Research (1989)

The pathophysiological effects of congestive heart failure and physiological effects of exercise training on skeletal muscle may be mediated in part by modulation of beta-adrenergic receptor density. To shed light on the physiological role of skeletal muscle beta-receptors, their density and distribution were characterized in muscle fibers and resistance arterioles of whole tissue slices of three rat hindquarter muscles differing markedly in fiber type composition and capacities for oxidative metabolism and vasodilatation. Binding isotherms and quantitative light microscopic autoradiographic localization of receptors were performed by incubating tissue slices in selected concentrations of [125I]cyanopindolol with and without 10(-5) M l-propranolol. Muscle fiber types were delineated in adjacent sections by histochemical staining of myofibrillar ATPase activity at pH 4.5-4.55. The total tissue content of receptors (Bmax) was nearly threefold greater in the soleus, a muscle consisting almost entirely of slow-twitch (type I) fibers than in superficial white vastus lateralis, a muscle composed of greater than 95% fast-twitch (type IIb) fibers. Bmax was intermediate in gastrocnemius, a mixed fiber muscle (all differences p less than 0.01). Receptor affinity for radioligand was higher in the white vastus than in the mixed fiber and slow-twitch muscles (Kd = 3.5 +/- 0.4 pM for white vastus versus 6.8 +/- 0.8 and 6.4 +/- 1.1 pM in gastrocnemius and soleus, respectively; both p less than 0.01 versus white vastus). Disparities in Bmax among muscles were due entirely to differences in receptor densities of skeletal muscle cells as shown autoradiographically. Furthermore, variations in Bmax of the three skeletal muscles were directly related to percentage of type I fibers (r = 0.99; p less than 0.001), which had a beta-receptor density that was approximately 4.5-fold greater than in superficially located type IIb fibers, 3.2-fold greater than in intermediate depth type IIb fibers, and 2.0-fold greater than in type IIa fibers. In contrast, grain densities of resistance arterioles were similar regardless of surrounding skeletal muscle fiber type composition. However, resistance arterioles were 2.5- and 6.1-fold more numerous in the slow-twitch soleus than in the gastrocnemius and superficial white vastus, respectively (all differences p less than 0.01). We conclude that beta-receptor density of rat hindquarter skeletal muscles is directly proportional to percentage of slow-twitch fibers, while receptor affinity for antagonist is higher in fast-twitch than in slow-twitch or mixed fiber muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
Risk Factors for Recurrent Diabetic Foot Ulcers
Authors: Edgar J.G. Peters, David G. Armstrong, Lawrence A. Lavery
Journal: Diabetes Care (2007)

The rate of recurrent ulceration in diabetic patients with a history of foot complications is high (1–6). The purpose of this study was to evaluate the outcome of diabetic foot ulcers and to study the risk factors for recurrent foot ulcers in a high-risk setting such as a specialized tertiary diabetic foot center.

The study was set up as a prospective cohort study to evaluate risk factors for secondary diabetic foot ulcers. At enrollment, 81 subjects presented with an ulcer distal to the ankle and were sequentially enrolled from a high-risk foot clinic at an urban teaching institution. Patients without follow-up visit at the diabetic foot clinic were excluded from the study. All patients were assessed at the foot clinic at intervals necessary for either treatment or for regular care according to international standards (7). Part of the data of this cohort of patients has been previously published (8). Tactile, vibratory nerve function, three-step mean plantar pressure, range of motion, and multiple vascular parameters were assessed using previously described techniques (1,9–11). Plantar peak pressures >70 N/cm2 were defined as elevated (1,3,8,12–15).

The presence of risk factors in the group of patients that developed an ulcer in the follow-up period was compared with the presence of these factors in the group of patients without a …