tbuckley/cabot-search huggingface dataset:
Hormone Replacement Therapy and Prevention of Nonvertebral Fractures
Authors: David J. Torgerson, Sally E. M. Bell-Syer
Journal: JAMA (2001)

ContextHormone replacement therapy (HRT) is widely considered to reduce fractures, but this belief is based on observational data; evidence from randomized trials is lacking.ObjectiveTo conduct a systematic review of all randomized trials of HRT that have reported or collected nonvertebral fracture data but that may not have focused on fracture prevention.Data SourcesThe MEDLINE, EMBASE, Science Citation Index, and Cochrane Controlled Trials Register databases were searched from 1997 through 2000 and a search was conducted of all recent systematic reviews to identify older studies. Authors were contacted to establish whether fracture data had been collected but not reported. Researchers in the field and pharmaceutical companies also were contacted to try to identify unpublished studies.Study SelectionTrials were included in which participants had been randomized to at least 12 months of therapy and data on nonvertebral fractures at any other site and due to any cause were available. Of 70 initially identified studies, 22 were included in the analysis.Data ExtractionBoth investigators extracted data independently and appraised trial quality according to the Jadad scale, which assesses the methods of randomization, concealment allocation, and reporting of withdrawals and dropouts. Disagreements were resolved by discussion.Data SynthesisThere was an overall 27% reduction in nonvertebral fractures in a pooled analysis (reduction favoring HRT in relative risk [RR], 0.73; 95% confidence interval [CI], 0.56-0.94; P = .02). This effect was greater among women randomized to HRT who had a mean age younger than 60 years (RR, 0.67; 95% CI, 0.46-0.98; P = .03). Among women with a mean age of 60 years or older, there was a reduced effect (RR, 0.88; 95% CI, 0.71-1.08; P = .22). For hip and wrist fractures alone, the effectiveness of HRT appeared more marked (RR, 0.60; 95% CI, 0.40-0.91; P = .02), particularly for women younger than 60 years (RR, 0.45; 95% CI, 0.26-0.79; P = .005).ConclusionsOur meta-analysis of randomized controlled trials of HRT noted a statistically significant reduction in nonvertebral fractures. However, this effect may be attenuated in older women.
Pyogenic bacterial lower respiratory tract infection in human immunodeficiency virus-infected patients
Authors: C. Mayaud, A. Parrot, J. Cadranel
Journal: European Respiratory Journal (2002)

In human immunodeficiency virus (HIV)-infected patients, bacterial lower respiratory tract infections are the most frequent respiratory diseases. They are frequently the first clinical manifestation of HIV infection. The incidence and severity of bacterial lower respiratory tract infections increase with the degree of immunosuppression. At the acquired immune deficiency syndrome (AIDS) stage, the responsible bacteria and clinical presentation may be atypical. Bacterial pneumonia may be fatal, particularly in AIDS patients, and its occurrence is predictive of a reduced survival time. Pneumococcal vaccine is recommended in patients with a CD4 T‐lymphocyte count of &gt;200 cells·mm −3 and cotrimoxazole (trimethoprim/sulfamethoxazole) in patients with a CD4 T‐lymphocyte count of &lt;200 cells·mm −3 . Unfortunately, such prophylaxis remains insufficiently prescribed and its protective effect is limited. Highly active antiretroviral treatment has dramatically reduced the incidence of lower respiratory tract infection due to Pseudomonas aeruginosa and opportunistic bacteria. In contrast, successful highly active antiretroviral therapy slightly decreased the risk of bacterial pneumonia due to usual bacteria, even in patients on successful highly active antiretroviral therapy.
Parallel evolution of conserved non-coding elements that target a common set of developmental regulatory genes from worms to humans.
Authors: Tanya Vavouri, Klaudia Walter, Walter R Gilks, Ben Lehner, Greg Elgar
Journal: Genome biology (2007)

The human genome contains thousands of non-coding sequences that are often more conserved between vertebrate species than protein-coding exons. These highly conserved non-coding elements (CNEs) are associated with genes that coordinate development, and have been proposed to act as transcriptional enhancers. Despite their extreme sequence conservation in vertebrates, sequences homologous to CNEs have not been identified in invertebrates.
Severity of obstructive sleep apnoea/hypopnoea syndrome and subsequent waking EEG spectral power
Authors: J. Grenèche, M. Sarémi, C. Erhardt, A. Hoeft, A. Eschenlauer, A. Muzet, P. Tassi
Journal: European Respiratory Journal (2008)

It is well known that most patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS) suffer sleepiness, although the underlying mechanisms of this relationship remain unclear. The present study examined the relationship between nocturnal variables and the subsequent waking electroencephalogram (EEG), in order to determine if sleepiness was related to OSAHS severity and due to sleep fragmentation or to nocturnal hypoxaemia. In total, 12 moderate-to-severe OSAHS patients underwent a total sleep night followed by a 24-h period of sustained wakefulness where the waking EEG was measured every hour. The results showed that alpha (7.9–12.6 Hz) and beta (12.7–29.2 Hz) activities were strongly related to OSAHS severity, mainly reflected by the apnoea index. Moreover, spectral power in most of the waking EEG components was significantly correlated with nocturnal hypoxaemia indices, namely alpha and beta activity when hypoxaemia becomes severe. However, no correlation was found between the waking EEG and sleep fragmentation parameters. In conclusion, the present results suggest that the difficulty in maintaining an optimal level of alertness, reflected by a higher activity in awake alpha and beta bands (7.9–29.2 Hz) in obstructive sleep apnoea/hypopnoea syndrome, was better explained by: 1) the apnoea as opposed to the hypopnoea index; and 2) nocturnal hypoxaemia as opposed to sleep fragmentation.
Maturity-Onset Diabetes of the Young (MODY) Mutation in Type 2 Diabetes and Latent Autoimmune Diabetes of the Adult
Authors: James McKinney, Henian Cao, Margaret T. Behme, Jeffrey L. Mahon, Robert A. Hegele
Journal: Diabetes Care (2003)

Owen et al. (1) reported etiologic heterogeneity among 268 subjects with type 2 diabetes, of whom ∼10% had autoantibodies and ∼1% had mutations in HNF1A (MODY3) encoding hepatic nuclear factor-1α. We hypothesized that maturity-onset diabetes of the young (MODY) gene mutations would also be found in subjects with latent autoimmune diabetes of the adult (LADA) (2). We studied 37 Canadian subjects diagnosed with LADA (of whom 20 were female) and …
Differentiating between Memory and Effector Cd8 T Cells by Altered Expression of Cell Surface O-Glycans
Authors: Laurie E. Harrington, Marisa Galvan, Linda G. Baum, John D. Altman, Rafi Ahmed
Journal: The Journal of Experimental Medicine (2000)

Currently there are few reliable cell surface markers that can clearly discriminate effector from memory T cells. To determine if there are changes in O-glycosylation between these two cell types, we analyzed virus-specific CD8 T cells at various time points after lymphocytic choriomeningitis virus infection of mice. Antigen-specific CD8 T cells were identified using major histocompatibility complex class I tetramers, and glycosylation changes were monitored with a monoclonal antibody (1B11) that recognizes O-glycans on mucin-type glycoproteins. We observed a striking upregulation of a specific cell surface O-glycan epitope on virus-specific CD8 T cells during the effector phase of the primary cytotoxic T lymphocyte (CTL) response. This upregulation showed a strong correlation with the acquisition of effector function and was downregulated on memory CD8 T cells. Upon reinfection, there was again increased expression of this specific O-glycan epitope on secondary CTL effectors, followed once more by decreased expression on memory cells. Thus, this study identifies a new cell surface marker to distinguish between effector and memory CD8 T cells. This marker can be used to isolate pure populations of effector CTLs and also to determine the proportion of memory CD8 T cells that are recruited into the secondary response upon reencounter with antigen. This latter information will be of value in optimizing immunization strategies for boosting CD8 T cell responses.
Angiotensin II-induced hypertrophy of cultured murine proximal tubular cells is mediated by endogenous transforming growth factor-beta.
Authors: G Wolf, E Mueller, R A Stahl, F N Ziyadeh
Journal: Journal of Clinical Investigation (1993)

Previous studies by our group have demonstrated that angiotensin II (ANG II), as a single factor in serum-free medium, induces cellular hypertrophy of a cultured murine proximal tubular cell line (MCT). The present study was performed to test the hypothesis that this growth effect was mediated by activation of endogenous transforming growth factor-beta (TGF-beta). Exogenous TGF-beta 1 (1 ng/ml) mimicked the growth effects observed with 10(-8) M ANG II (inhibition of DNA synthesis and induction of cellular hypertrophy). A neutralizing anti-TGF-beta antibody attenuated the ANG II-induced increase in de novo protein and total RNA synthesis as well as total protein content. This antibody also abolished the ANG II-mediated inhibition of [3H]thymidine incorporation into quiescent MCT cells. Control IgG or an unrelated antibody had no effect. A bioassay for TGF-beta using mink lung epithelial cells revealed that MCT cells treated with ANG II released active TGF-beta into the cell culture supernatant. Northern blot analysis and semi-quantitative cDNA amplification demonstrated increases in steady-state levels for TGF-beta 1 mRNA after ANG II stimulation of MCT cells, but not in a syngeneic murine mesangial cell line. Our data indicate that the ANG II-induced hypertrophy in MCT cells is mediated by synthesis and activation of endogenous TGF-beta. It is intriguing to speculate that TGF-beta may play a role in the early tubular cell hypertrophy and the subsequent interstitial scarring observed in several models of chronic renal injury that are characterized by increased activity of intrarenal ANG II.
Simultaneous administration of thromboxane A2- and serotonin S2-receptor antagonists markedly enhances thrombolysis and prevents or delays reocclusion after tissue-type plasminogen activator in a canine model of coronary thrombosis.
Authors: P Golino, J H Ashton, J McNatt, P Glas-Greenwalt, S K Yao, R A O'Brien, L M Buja, J T Willerson
Journal: Circulation (1989)

Dynamic changes of the thrombus after its formation due to platelet activation may affect the speed of thrombolysis. In the present study, we wanted to evaluate the role played by thromboxane A2 (TXA2) and serotonin (5HT) in mediating platelet activation during lysis of intracoronary thrombi with human recombinant tissue-type plasminogen activator (t-PA). Coronary thrombi were induced in 26 anesthetized, open-chest dogs by inserting a copper coil into the left anterior descending coronary artery (LAD). LAD blood flow was monitored throughout the experiment by means of a Doppler flow probe placed proximally to the coil. Presence of the thrombus was documented for 30 minutes. The dogs were then assigned to one of four groups as follows: group 1 dogs (n = 8), serving as controls, received a bolus of heparin (200 units/kg) and a bolus of t-PA (80 micrograms/kg) followed by a continuous infusion (8 micrograms/kg/min) for up to 90 minutes or until reperfusion was achieved; group 2 dogs (n = 10) received, immediately before heparin and t-PA, an intravenous bolus of SQ29548 (SQ) (0.4 mg/kg, a selective TXA2-receptor antagonist) and LY53857 (LY) (0.2 mg/kg, a selective serotonin S2-receptor antagonist); group 3 dogs (n = 7) received, before heparin and t-PA, an intravenous bolus of SQ alone (0.4 mg/kg); and group 4 dogs (n = 7) received, before heparin and t-PA, an intravenous bolus of LY alone (0.2 mg/kg). After thrombolysis, all dogs were monitored for 90 minutes or until a persistent reocclusion occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
Cor pulmonale in an adult secondary to Niemann-Pick disease.
Authors: A M Lever, J B Ryder
Journal: Thorax (1983)

<h3>Background</h3> Trichlorophenols (TCPs) are organochlorine compounds which are ubiquitous in the environment and well known for their carcinogenic effects. However, little is known about their neurotoxicity in humans. <h3>Objectives</h3> Our goal was to examine the association between body burden of TCPs (ie, 2,4,5-TCP and 2,4,6-TCP) and attention deficit hyperactivity disorder (ADHD). <h3>Methods</h3> We calculated ORs and 95% CIs from logistic regression analyses using data from the 1999–2004 National Health and Nutrition Examination Survey (NHANES) to evaluate the association between urinary TCPs and parent-reported ADHD among 2546 children aged 6–15 years. <h3>Results</h3> Children with low levels (&lt;3.58 μg/g) and high levels (≥3.58 μg/g) of urinary 2,4,6-TCP had a higher risk of parent-reported ADHD compared to children with levels below the limit of detection (OR 1.54, 95% CI 0.97 to 2.43 and OR 1.77, 95% CI 1.18 to 2.66, respectively; p for trend=0.006) after adjusting for covariates. No association was found between urinary 2,4,5-TCP and parent-reported ADHD. <h3>Conclusion</h3> Exposure to TCP may increase the risk of behavioural impairment in children. The potential neurotoxicity of these chemicals should be considered in public health efforts to reduce environmental exposures/contamination, especially in countries where organochlorine pesticides are still commonly used.
Longchain n−3 polyunsaturated fatty acids and blood vessel function
Authors: M Abeywardena
Journal: Cardiovascular Research (2001)

The cardiovascular health benefits of longchain n−3 polyunsaturated fatty acids (PUFAs) have been reported to exert at several different cellular control mechanisms. These include, effects on lipoprotein metabolism, haemostatic function, platelet/vessel wall interactions, anti-arrhythmic actions and also inhibition of proliferation of smooth muscle cells and therefore growth of the atherosclerotic plaque. Fish oil feeding has also been found to result in moderate reductions in blood pressure and to modify vascular neuroeffector mechanisms. The majority of such cardiovascular benefits of n−3 PUFAs are likely to be mediated in the vascular wall and at the vascular endothelium level, since this monolayer of cells plays a central role in the regulation and maintenance of cardiovascular homeostasis and function. While these processes include endothelium-derived vasorelaxant and vasoconstrictor compounds, the vascular endothelium also plays host to many receptors, binding proteins, transporters and signalling mechanisms. Accordingly, endothelial dysfunction, which underlies many cardiovascular disease conditions, can trigger acute vascular events including vasospasm, thrombosis or restenosis leading to ischaemia. The longchain n−3 PUFAs have been reported to possess several properties that may positively influence vascular function. These include favourable mediator profiles (nitric oxide, eicosanoids) that influence vascular reactivity, change in vascular tone via actions on selective ion channels, and maintenance of vascular integrity. In addition to direct effects on contractility, n−3 PUFAs may affect vascular function, and the process of atherogenesis, via inhibition of vascular smooth muscle cell proliferation at the gene expression level, and by modifying expression of inflammatory cytokinesis and adhesion molecules. Collectively, these properties are consistent with pleiotropic actions of longchain n−3 PUFAs, and may explain the beneficial cardiovascular protection of this family of fatty acids that have been clearly evident through epidemiological data as well from more recent large-scale clinical trials.
Assessment of Transmyocardial Perfusion in Alligator Hearts
Authors: Takushi Kohmoto, Michael Argenziano, Noriyoshi Yamamoto, Kent A. Vliet, Anguo Gu, Carolyn M. DeRosa, Peter E. Fisher, Henry M. Spotnitz, Daniel Burkhoff, Craig R. Smith
Journal: Circulation (1997)

Background Techniques for achieving myocardial perfusion directly from the left ventricular chamber are currently under investigation. Although originally based on the anatomy of reptilian hearts, which are rich in transmural channels and reported to have a poorly developed coronary vasculature, the blood flow capacity of a transmyocardial blood supply has not been studied in these hearts. With the ultimate goal of providing insight into the potential for achieving transmyocardial perfusion in human hearts, we studied the relative contribution of transmyocardial and coronary perfusion in alligator hearts. Methods and Results After explantation from six American alligators, the left ventricle was instrumented, and coronary arteries were perfused with oxygenated physiological solution. Using microspheres to estimate regional myocardial perfusion in the beating hearts, we show that although the epicardium was well perfused by the coronary arteries (0.20±0.08 versus 0.07±0.01 mL·min −1 ·g −1 owing to flow from the ventricular chamber), a significant proportion of endocardial perfusion was from the ventricular chamber (0.21±0.07 mL·min −1 ·g −1 from the left ventricle versus 0.13±0.04 mL·min −1 ·g −1 from coronary arteries). Conclusions A significant amount of direct transmyocardial perfusion is present in alligator hearts. The conditions that apparently permit this situation in reptilian hearts are reviewed, and their implications for aiding in the optimization of techniques for achieving transmyocardial flow in humans are discussed.
Benefits of Supplemental Oxygen in Exercise Training in Nonhypoxemic Chronic Obstructive Pulmonary Disease Patients
Authors: Margareta Emtner, Janos Porszasz, Mary Burns, Attila Somfay, Richard Casaburi
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Supplemental oxygen improves exercise tolerance of normoxemic and hypoxemic chronic obstructive pulmonary disease (COPD) patients. We determined whether nonhypoxemic COPD patients undergoing exercise training while breathing supplemental oxygen achieve higher intensity and therefore improve exercise capacity more than patients breathing air. A double-blinded trial was performed involving 29 nonhypoxemic patients (67 years, exercise SaO2 > 88%) with COPD (FEV1 = 36% predicted). All exercised on cycle ergometers for 45 minutes, 3 times per week for 7 weeks at high-intensity targets. During exercise, they received oxygen (3 L/minute) (n = 14) or compressed air (3 L/minute) (n = 15). Both groups had a higher exercise tolerance after training and when breathing oxygen. However, the oxygen-trained group increased the training work rate more rapidly than the air-trained group. The mean +/- SD work rate during the last week was 62 +/- 19 W (oxygen-trained group) and 52 +/- 22 W (air-trained group) (p < 0.01). After training, endurance in constant work rate tests increased more in the oxygen-trained group (14.5 minutes) than in the air-trained group (10.5 minutes) (p < 0.05). At isotime, the breathing rate decreased four breaths per minute in the oxygen-trained group and one breath per minute in the air-trained group (p = 0.001). We conclude that supplemental oxygen provided during high-intensity training yields higher training intensity and evidence of gains in exercise tolerance in laboratory testing.
Active chloride secretion in the normal human jejunum.
Authors: G R Davis, C A Santa Ana, S Morawski, J S Fordtran
Journal: Journal of Clinical Investigation (1980)

To determine whether the small intestine normally secretes fluid, it would be necessary to reduce or inhibit the greater absorptive processes that would otherwise mask such secretion if present. To do this, we perfused bicarbonate-free solutions in the jejunum of normal subjects, because it has been shown that active absorption from this part of the human small intestine is dependent on luminal bicarbonate. We found that the jejunum did secrete sodium chloride and water when isotonic bicarbonate-free solutions were perfused. Further studies revealed that the sodium secretion was passive, but that chloride was secreted against an electrochemical gradient and that observed chloride flux ratios did not agree with the flux ratios calculated for passive chloride movement. We conclude, therefore, that the normal jejunum actively secretes chloride, but that this is masked by greater absorptive processes when balanced electrolyte solutions are perfused. The rate of this active chloride secretion may be one of the factors that regulate the rate of fluid absorption in the normal human intestine.
Clinical Applications of Brain-Computer Interfaces: Current State and Future Prospects
Authors: J.N. Mak, J.R. Wolpaw
Journal: IEEE Reviews in Biomedical Engineering (2009)

Braincomputer interfaces (BCIs) allow their users to communicate or control external devices using brain signals rather than the brain's normal output pathways of peripheral nerves and muscles. Motivated by the hope of restoring independence to severely disabled individuals and by interest in further extending human control of external systems, researchers from many fields are engaged in this challenging new work. BCI research and development has grown explosively over the past two decades. Efforts have begun recently to provide laboratory-validated BCI systems to severely disabled individuals for real-world applications. In this paper, we discuss the current status and future prospects of BCI technology and its clinical applications. We will define BCI, review the BCI-relevant signals from the human brain, and describe the functional components of BCIs. We will also review current clinical applications of BCI technology and identify potential users and potential applications. Lastly, we will discuss current limitations of BCI technology, impediments to its widespread clinical use, and expectations for the future.