tbuckley/cabot-search huggingface dataset:
Ventilatory muscle strength and endurance in myasthenia gravis
Authors: SP Keenan, D Alexander, JD Road, CF Ryan, J Oger, PG Wilcox
Journal: European Respiratory Journal (1995)

Patients with generalized myasthenia gravis (MG) often have associated ventilatory muscle involvement. It is not known whether patients with isolated ocular muscle involvement have identifiable involvement of their ventilatory muscles. Most studies have assessed muscle involvement by measuring muscle strength; however, we hypothesized that measures of ventilatory muscle endurance may be more sensitive tests of ventilatory muscle involvement in myasthenia gravis. We studied 17 patients with myasthenia gravis (four with ocular involvement alone and 13 with varying degrees of generalized myasthenia gravis). Spirometry, ventilatory muscle strength (maximum inspiratory and expiratory pressures (MIP and MEP)) and endurance (2 min incremental threshold loading test) were measured before and 20 min after i.m. neostigmine. We compared the results with those of 10 normal controls. We found no difference between patients with isolated ocular involvement and controls. Ocular myasthenia gravis patients did not improve after neostigmine. The patients with generalized myasthenia gravis had reduced baseline ventilatory muscle strength (MIP 67 cmH2O (70% of predicted), MEP 86 cmH2O (50% of pred) and endurance (mean maximal load achieved = 246 g, mean pressure at highest load (P) = 19.4 cmH2O) compared with controls. After neostigmine, there was a significant increase in MIP in patients with generalized myasthenia gravis and a trend towards an increased MEP. As a group, the patients with generalized myasthenia gravis did not demonstrate a change in their ventilatory muscle endurance after neostigmine; however, there was considerable interpatient variability in response. We conclude that patients with isolated ocular MG have normal ventilatory muscle strength when tested conventionally.(ABSTRACT TRUNCATED AT 250 WORDS)
Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease
Authors: Manuel A. Rivas, Mélissa Beaudoin, Agnes Gardet, Christine Stevens, Yashoda Sharma, Clarence K. Zhang, Gabrielle Boucher, Stephan Ripke, David Ellinghaus, Noel Burtt, Tim Fennell, Andrew Kirby, Anna Latiano, Philippe Goyette, Todd Green, Jonas Halfvarson, Talin Haritunians, Joshua M. Korn, Finny Kuruvilla, Caroline Lagacé, Benjamin Neale, Ken Sin Lo, Phil Schumm, Leif Törkvist, Marla C. Dubinsky, Steven R. Brant, Mark S. Silverberg, Richard H. Duerr, David Altshuler, Stacey Gabriel, Guillaume Lettre, Andre Franke, Mauro D'Amato, Dermot P.B. McGovern, Judy H. Cho, John D. Rioux, Ramnik J. Xavier, Mark J. Daly
Journal: Nature Genetics (2011)
Cognitive Trajectories after Postoperative Delirium
Authors: Jane S. Saczynski, Edward R. Marcantonio, Lien Quach, Tamara G. Fong, Alden Gross, Sharon K. Inouye, Richard N. Jones
Journal: New England Journal of Medicine (2012)

Delirium is common after cardiac surgery and may be associated with long-term changes in cognitive function. We examined postoperative delirium and the cognitive trajectory during the first year after cardiac surgery.We enrolled 225 patients 60 years of age or older who were planning to undergo coronary-artery bypass grafting or valve replacement. Patients were assessed preoperatively, daily during hospitalization beginning on postoperative day 2, and at 1, 6, and 12 months after surgery. Cognitive function was assessed with the use of the Mini-Mental State Examination (MMSE; score range, 0 to 30, with lower scores indicating poorer performance). Delirium was diagnosed with the use of the Confusion Assessment Method. We examined performance on the MMSE in the first year after surgery, controlling for demographic characteristics, coexisting conditions, hospital, and surgery type.The 103 participants (46%) in whom delirium developed postoperatively had lower preoperative mean MMSE scores than those in whom delirium did not develop (25.8 vs. 26.9, P<0.001). In adjusted models, those with delirium had a larger drop in cognitive function (as measured by the MMSE score) 2 days after surgery than did those without delirium (7.7 points vs. 2.1, P<0.001) and had significantly lower postoperative cognitive function than those without delirium, both at 1 month (mean MMSE score, 24.1 vs. 27.4; P<0.001) and at 1 year (25.2 vs. 27.2, P<0.001) after surgery. With adjustment for baseline differences, the between-group difference in mean MMSE scores was significant 30 days after surgery (P<0.001) but not at 6 or 12 months (P=0.056 for both). A higher percentage of patients with delirium than those without delirium had not returned to their preoperative baseline level at 6 months (40% vs. 24%, P=0.01), but the difference was not significant at 12 months (31% vs. 20%, P=0.055).Delirium is associated with a significant decline in cognitive ability during the first year after cardiac surgery, with a trajectory characterized by an initial decline and prolonged impairment. (Funded by the Harvard Older Americans Independence Center and others.).
Hepatitis B virus (HBV) reactivation with immunosuppressive therapy in rheumatic diseases: assessment and preventive strategies
Authors: L H Calabrese
Journal: Annals of the Rheumatic Diseases (2006)

Understanding of the natural history and basic biology of hepatitis B virus (HBV) has increased greatly in recent years. In view of this, the following are reviewed here: (a) recent advances in HBV biology pertinent to the rheumatic disease population; (b) the risks of HBV reactivation in patients with rheumatic disease undergoing immunosuppression; and (c) potential strategies to manage these risks.
Renin-Angiotensin-Aldosterone System and Progression of Renal Disease
Authors: Christiane Rüster, Gunter Wolf
Journal: Journal of the American Society of Nephrology (2006)

Inhibition of the renin-angiotensin-aldosterone system (RAAS) is one of the most powerful maneuvers to slow progression of renal disease. Angiotensin II (AngII) has emerged in the past decade as a multifunctional cytokine that exhibits many nonhemodynamic properties, such as acting as a growth factor and profibrogenic cytokine, and even having proinflammatory properties. Many of these deleterious functions are mediated by other factors, such as TGF-beta and chemoattractants that are induced in the kidney by AngII. Moreover, understanding of the RAAS has become much more complex in recent years with the identification of novel peptides (e.g., AngIV) that could bind to specific receptors, elucidating deleterious effects, and non-angiotensin-converting enzyme (ACE)-mediated generation of AngII. The ability of renal cells to produce AngII in a concentration that is much higher than what is found in the systemic circulation and the observation that aldosterone may be engaged directly in profibrogenic processes independent of hypertension have added to the complexity of the RAAS. Even renin has now been identified to have a "life on its own" and mediates profibrotic effects via binding to specific receptors. Finally, drugs that are used to block the RAAS, such as ACE inhibitors or certain AngII type 1 receptor antagonists, may have properties on cells independent of AngII (ACE inhibitor-mediated outside-inside signaling and peroxisome proliferator-activated receptor-gamma stimulatory effects of certain sartanes). Although blockade of the RAAS with ACE inhibitors, AngII type 1 receptor antagonists, or the combination of both should be part of every strategy to slow progression of renal disease, a better understanding of the novel aspects of the RAAS should contribute to the development of innovative strategies not only to completely halt progression but also to induce regression of human renal disease.
Nasal Inhalation as a Cause of Inefficient Pulmonal Aerosol Inhalation Technique in Children
Authors: Søren Pedersen, Poul Aabel ØTergaard
Journal: Allergy (1983)

In order to evaluate whether children can be taught the efficient use of a pressurized terbutaline aerosol with a tube spacer 71 children were given careful instruction in aerosol inhalation technique according to the manufacturer's instructions. Inhalation technique, was assessed as being efficient when a child achieved an increase of more than 19% in FEV 1 10 min after taking two puffs of terbutaline (each puff = 0.25 mg). After instruction about 37% of children aged 5–7 years and about 80% of children over 7 year were efficient in inhalation technique. Inhalation through the nose after actuation into the mouth accounted for about 50% of treatment failures, with the problem being more frequent in the younger age group. When this error was corrected about 83% of the children were efficient in the technique. Coordination problems and too rapid inspiration after actuation were also common errors. The findings stress the importance of checking all children's inhalation technique before prescribing inhalation therapy. Careful instruction was not enough. The possibility of nasal inhaling should be borne in mind when looking for causes of treatment failure.
Suppression of pulmonary innate host defence in smokers
Authors: C Herr, C Beisswenger, C Hess, K Kandler, N Suttorp, T Welte, J-M Schroeder, C Vogelmeier, R B. f. t. C. S. Group
Journal: Thorax (2008)

Smoking increases the susceptibility to pulmonary infection and is a risk factor for the development of chronic obstructive pulmonary disease (COPD). It is postulated that cigarette smoke suppresses the activation of the innate immune system in response to bacterial infection.Using sensitive ex vivo analysis, the level of the endogenous antibiotic peptide human beta-defensin-2 (hBD-2) was measured in pharyngeal washing fluid and sputum from patients with community acquired pneumonia. The regulation of antibacterial host defence molecules was studied in vitro. The effect of cigarette smoke on the antibacterial activity of differentiated airway epithelium and the expression of host defence molecules was studied in an in vitro infection model.Current or former smoking was associated with significantly reduced hBD-2 levels in pharyngeal washing fluid and sputum from patients with acute pneumonia. Exposure of airway epithelium to smoke in vitro inhibited the induction of hBD-2 by bacteria. This correlated with decreased antimicrobial activity. This effect was mimicked by hydrogen peroxide, and catalase blunted the smoke-induced inhibition of epithelial host defence.Smoke exposure suppresses the induction of epithelial antibacterial host defences. These findings link smoking with increased susceptibility to infection. This mechanism may be important in the pathogenesis of pneumonia and COPD.
Genome-Wide Association Study of Survival in Non–Small Cell Lung Cancer Patients Receiving Platinum-Based Chemotherapy
Authors: Xifeng Wu, Yuanqing Ye, Rafael Rosell, Christopher I. Amos, David J. Stewart, Michelle A.T. Hildebrandt, Jack A. Roth, John D. Minna, Jian Gu, Jie Lin, Shama C. Buch, Tomoko Nukui, Jose Luis Ramirez Serrano, Miquel Taron, Adrian Cassidy, Charles Lu, Joe Y. Chang, Scott M. Lippman, Waun Ki Hong, Margaret R. Spitz, Marjorie Romkes, Ping Yang
Journal: JNCI Journal of the National Cancer Institute (2011)

BackgroundInterindividual variation in genetic background may influence the response to chemotherapy and overall survival for patients with advanced-stage non–small cell lung cancer (NSCLC).
Weakly acidic reflux in patients with chronic unexplained cough during 24 hour pressure, pH, and impedance monitoring
Authors: D Sifrim
Journal: Gut (2005)

During development, mitral cells, the major output neurons of the olfactory bulb, project their axons caudolaterally into the telencephalon and form the lateral olfactory tract (LOT). Two types of guidance cues have been suggested for this projection. First, a long-range factor Slit, which is secreted from the septum, repels mitral cell axons into a caudolateral direction. Second, the pathway of mitral cell axons contains a subset of neurons designated as lot cells, which guide the axons through short-range interactions. It is not clear how these two guidance cues relate to each other and how they share the physiological roles. Here we examined the behavior of mitral cell axons in organotypic culture on ectopic application of Slit and inhibition of endogenous Slit signaling. The results suggested that the short-range guidance cue in the LOT pathway functions independently from Slit. Furthermore, our results showed that removal of the septum and inhibition of Slit signaling did not affect the projection of mitral cell axons. Although the septum and exogenous Slit can repel olfactory bulb axons, our results cast doubts on the physiological relevance of the septum and endogenous Slit in guiding the projection of mitral cell axons.
Effects of Ischemia on Discontinuous Action Potential Conduction in Hybrid Pairs of Ventricular Cells
Authors: Ronald Wilders, E. Etienne Verheijck, Ronald W. Joyner, David A. Golod, Rajiv Kumar, Antoni C. G. van Ginneken, Lennart N. Bouman, Habo J. Jongsma
Journal: Circulation (1999)

Background —Acute ischemia often occurs in cardiac tissue that has prior injury, resulting in spatially inhomogeneous distributions of membrane properties and intercellular coupling. Changes in action potential conduction with ischemia, which can be associated with release of catecholamines, may be particularly important in tissue that has discontinuous conduction resulting from prior infarction, hypertrophy, or myopathy. Methods and Results —Isolated guinea pig ventricular myocytes were electrically coupled by a coupling-clamp circuit to a comprehensive computer model of a guinea pig ventricular myocyte to assess alterations in the critical value of coupling conductance required for action potential conduction from the real cell to the model cell when the real cell was exposed to a solution that included hypoxia, acidosis, and an elevated extracellular potassium concentration to simulate acute ischemia. The “ischemic” solution increased critical coupling conductance from 6.2±0.1 to 7.4±0.2 nS and decreased the associated maximum conduction delay from 31±1 to 23±1 ms (mean±SEM, n=11). The ischemic solution plus 1 μmol/L norepinephrine decreased critical coupling conductance from 5.9±0.2 to 5.0±0.1 nS and increased maximum conduction delay from 31±2 to 54±4 ms (mean±SEM, n=8). Conclusions —The release of catecholamines with ischemia, in a setting of partially uncoupled cells, may play a major role in producing long conduction delays, which may allow reentrant pathways.
Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens
Authors: Theresa L. Geiger, Michael C. Abt, Georg Gasteiger, Matthew A. Firth, Margaret H. O’Connor, Clair D. Geary, Timothy E. O’Sullivan, Marcel R. van den Brink, Eric G. Pamer, Alan M. Hanash, Joseph C. Sun
Journal: The Journal of Experimental Medicine (2014)

The bZIP transcription factor Nfil3 (also known as E4BP4) is required for the development of natural killer (NK) cells and type 1 innate lymphoid cells (ILC1s). We find that Nfil3 plays a critical role in the development of other mucosal tissue-associated innate lymphocytes. Type 3 ILCs (ILC3s), including lymphoid tissue inducer (LTi)–like cells, are severely diminished in both numbers and function in Nfil3-deficient mice. Using mixed bone marrow chimeric mice, we demonstrate that Nfil3 is critical for normal development of gut-associated ILC3s in a cell-intrinsic manner. Furthermore, Nfil3 deficiency severely compromises intestinal innate immune defense against acute bacterial infection with Citrobacter rodentium and Clostridium difficile. Nfil3 deficiency resulted in a loss of the recently identified ILC precursor, yet conditional ablation of Nfil3 in the NKp46+ ILC3 subset did not perturb ILC3 numbers, suggesting that Nfil3 is required early during ILC3 development but not for lineage maintenance. Lastly, a marked defect in type 2 ILCs (ILC2s) was also observed in the lungs and visceral adipose tissue of Nfil3-deficient mice, revealing a general requirement for Nfil3 in the development of all ILC lineages.
Factors determining maximum inspiratory flow and maximum expiratory flow of the lung
Authors: J. Jordanoglou, N. B. Pride
Journal: Thorax (1968)

The factors determining maximum expiratory flow and maximum inspiratory flow of the lung are reviewed with particular reference to a model which compares the lung on forced expiration to a Starling resistor. The theoretical significance of the slope of the expiratory maximum flow-volume curve is discussed. A method of comparing maximum expiratory flow with maximum inspiratory flow at similar lung volumes is suggested; this may be applied either to a maximum flow-volume curve or to a forced expiratory and inspiratory spirogram.
Repair of 2′-<i>C</i>-Cyano-2′-Deoxy-1-β-<scp>d</scp>-<i>arabino</i>-Pentofuranosylcytosine–Induced DNA Single-Strand Breaks by Transcription-Coupled Nucleotide Excision Repair
Authors: Yaqing Wang, Xiaojun Liu, Akira Matsuda, William Plunkett
Journal: Cancer Research (2008)

Abstract The cytosine nucleoside analogue 2′-C-cyano-2′-deoxy-1-β-d-arabino-pentofuranosylcytosine (CNDAC) causes DNA single-strand breaks after its incorporation into DNA. This investigation sought to determine if DNA excision repair pathways were activated to repair this damage. Neither the base excision repair nor the mismatch repair pathway seemed to be involved. Cells deficient in the CSB protein, which initiates transcription-coupled nucleotide excision repair (NER) pathway (TC-NER), exhibited increased clonogenic sensitivity to CNDAC, whereas cells deficient in XPC, which initiates global genome NER, were slightly resistant relative to wild-type cells. The cells lacking either helicase XPB, which unwinds 5′ of the lesion, or endonuclease XPF, which incises 5′ to a lesion, exhibited increased clonogenic sensitivity to CNDAC, as did cells lacking the XPF partner protein ERCC1. This sensitization was independent of p53 function. Repletion of XPF restored sensitivity comparable with the wild type. In contrast, cells lacking either XPD, the 3′-helicase, or the 3′-endonuclease XPG were equally as sensitive as wild-type cells. In comparison, cells deficient in XPF were not sensitized to other cytosine nucleoside analogues, troxacitabine and cytarabine. Thus, the single-strand nick caused by CNDAC is recognized and, in part, repaired by the TC-NER pathway. NER proteins that function in the 5′ direction relative to the UV-induced lesion also participate in the repair of the CNDAC-induced nick, in contrast to proteins that process on the 3′ side of the lesion. [Cancer Res 2008;68(10):3881–9]
Plasma leptin levels and cardiac sympathetic function in patients with obstructive sleep apnoea-hypopnoea syndrome
Authors: K Shimizu
Journal: Thorax (2002)

Background: The control of body weight and cardiac sympathetic function in patients with obstructive sleep apnoea-hypopnoea syndrome (OSAHS) are important because both factors have significant effects on the mortality of these patients. It has recently been reported that OSAHS has a significant effect on the secretion of leptin, a hormone involved in the control of body weight and sympathetic nerve activity. In addition to the circadian rhythm of leptin secretion, the effects of one night of treatment with nasal continuous positive airway pressure (nCPAP) and the mechanism of the effects of nCPAP on nocturnal leptin secretion in patients with OSAHS has not yet been elucidated. Methods: Blood samples were obtained at 21.00 hours, 00.00 hours, 03.00 hours, and 06.30 hours from 21 subjects with OSAHS (mean apnoea and hypopnoea index 52.4/h), with and without nCPAP treatment. Iodine-123 (I<sup>123</sup>)-meta-iodobenzylguanidine (MIBG) imaging was used to evaluate myocardial sympathetic function before nCPAP treatment. Results: Plasma leptin reached a peak level at 00:00 hours (p&lt;0.01) in patients with OSAHS, both with and without nCPAP treatment. The first night of nCPAP treatment significantly decreased the plasma leptin levels at 03.00 hours (without nCPAP: mean (SE) 21.6 (4.7) ng/ml; with nCPAP: 19.3 (4.1) ng/ml, p&lt;0.02) and at 06.30 hours (without nCPAP: 17.6 (3.8) ng/ml; with nCPAP: 15.2 (3.2) ng/ml, p&lt;0.01). The magnitude of the decrease in leptin levels after nCPAP treatment was significantly correlated with cardiac sympathetic function measured before nCPAP treatment (p&lt;0.03). Conclusions: Patients with OSAHS undergo nocturnal increases in leptin levels in spite of interruption of sleep due to apnoea and hypopnoea, a trend seen in normal subjects. Plasma leptin levels in patients with OSAHS decreased significantly after the first night of nCPAP treatment. Enhanced cardiac sympathetic function in these patients may contribute to the leptin levels before nCPAP treatment and vice versa.
Two‐Photon Ratiometric Fluorescent Mapping of Intracellular Transport Pathways of pH‐Responsive Block Copolymer Micellar Nanocarriers
Authors: Tao Liu, Jinming Hu, Zhenyu Jin, Fan Jin, Shiyong Liu
Journal: Advanced Healthcare Materials (2013)

Ultrasensitive ratiometric fluorescent pH probes based on dual dye-labeled pH-responsive diblock copolymer micellar scaffold are constructed. The pH-sensitive emitting nature of BTPE dyes and emission turn-on of CMA moieties triggered by pH-actuated micelle-to-unimer of diblock scaffold synergistically contribute to the observed ≈250-fold changes of BTPE/CMA emission intensity ratios in the whole pH range. Two-photon ratiometric fluorescent pH mapping of intracellular gradients subjected by pH-responsive micellar nanoparticles in their endocytic pathway has been thus achieved. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Continued Pyrexia in Phthisis, Accompanied by Increase of Weight
Authors: C. T. Williams
Journal: BMJ (1872)

Hamatxde.-Inthese cases, where menorrhagia is dependent upon estravasation of blood in the pelvis-generally in Douglas's pouch-the history of its coming on at a menstrual period, frequently from over- exertion, accompanied by severe pain and often great prostration, will assist us materially in the diagnosis.Absolute rest, with ice to the abdomen, opium internally, or in form of suppository, subcutaneous injection of morphia, brandy or champagne to counteract the exhaustion and prevent death from prostration, will generally succeed in affording relieF.Puncturing the effused mass of blood is very seldom called for at first, and is more likely to induce further extravasation.Retained Products of Conceq)tion.-Casesfrequently occur in which