tbuckley/cabot-search huggingface dataset:
Mindfulness Meditation and Improvement in Sleep Quality and Daytime Impairment Among Older Adults With Sleep Disturbances
Authors: David S. Black, Gillian A. O’Reilly, Richard Olmstead, Elizabeth C. Breen, Michael R. Irwin
Journal: JAMA Internal Medicine (2015)

<h3>Importance</h3> Sleep disturbances are most prevalent among older adults and often go untreated. Treatment options for sleep disturbances remain limited, and there is a need for community-accessible programs that can improve sleep. <h3>Objective</h3> To determine the efficacy of a mind-body medicine intervention, called mindfulness meditation, to promote sleep quality in older adults with moderate sleep disturbances. <h3>Design, Setting, and Participants</h3> Randomized clinical trial with 2 parallel groups conducted from January 1 to December 31, 2012, at a medical research center among an older adult sample (mean [SD] age, 66.3 [7.4] years) with moderate sleep disturbances (Pittsburgh Sleep Quality Index [PSQI] &gt;5). <h3>Interventions</h3> A standardized mindful awareness practices (MAPs) intervention (n = 24) or a sleep hygiene education (SHE) intervention (n = 25) was randomized to participants, who received a 6-week intervention (2 hours per week) with assigned homework. <h3>Main Outcomes and Measures</h3> The study was powered to detect between-group differences in moderate sleep disturbance measured via the PSQI at postintervention. Secondary outcomes pertained to sleep-related daytime impairment and included validated measures of insomnia symptoms, depression, anxiety, stress, and fatigue, as well as inflammatory signaling via nuclear factor (NF)–κB. <h3>Results</h3> Using an intent-to-treat analysis, participants in the MAPs group showed significant improvement relative to those in the SHE group on the PSQI. With the MAPs intervention, the mean (SD) PSQIs were 10.2 (1.7) at baseline and 7.4 (1.9) at postintervention. With the SHE intervention, the mean (SD) PSQIs were 10.2 (1.8) at baseline and 9.1 (2.0) at postintervention. The between-group mean difference was 1.8 (95% CI, 0.6-2.9), with an effect size of 0.89. The MAPs group showed significant improvement relative to the SHE group on secondary health outcomes of insomnia symptoms, depression symptoms, fatigue interference, and fatigue severity (<i>P</i> &lt; .05 for all). Between-group differences were not observed for anxiety, stress, or NF-κB, although NF-κB concentrations significantly declined over time in both groups (<i>P</i> &lt; .05). <h3>Conclusions and Relevance</h3> The use of a community-accessible MAPs intervention resulted in improvements in sleep quality at immediate postintervention, which was superior to a highly structured SHE intervention. Formalized mindfulness-based interventions have clinical importance by possibly serving to remediate sleep problems among older adults in the short term, and this effect appears to carry over into reducing sleep-related daytime impairment that has implications for quality of life. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01534338
Effect of forced expirations on mucus clearance in patients with chronic airflow obstruction: effect of lung recoil pressure.
Authors: C P van der Schans, D A Piers, H Beekhuis, G H Koeter, T W van der Mark, D S Postma
Journal: Thorax (1990)

Spontaneous mucus clearance and the effect of forced expirations and coughing on mucus clearance were investigated in eight patients with chronic airflow obstruction and low elastic recoil pressure (emphysema group: mean FEV1 45% predicted) and in seven patients with chronic airflow obstruction and normal elastic recoil pressure (chronic bronchitis group: mean FEV1 57% predicted). Mucus clearance was measured in a central and a peripheral lung region by a radioactive aerosol tracer technique. Spontaneous mucus clearance from the peripheral lung region was higher in the patients with emphysema than in those with chronic bronchitis. There was no difference in central mucus clearance between the two groups. Mucus clearance from the peripheral lung region increased significantly during forced expirations and coughing in the patients with chronic bronchitis but not in those with emphysema. It is concluded that in patients with chronic airflow obstruction and regular sputum production spontaneous peripheral mucus clearance is greater in those with decreased elastic recoil pressure. Physiotherapy that includes forced expirations and coughing can enhance mucus clearance in such patients when elastic recoil pressure is normal but is unlikely to be effective when elastic recoil pressure is decreased.
Uncoupling of Vascular Endothelial Growth Factor with Nitric Oxide as a Mechanism for Diabetic Vasculopathy
Authors: Takahiko Nakagawa, Waichi Sato, Yuri Y. Sautin, Olena Glushakova, Byron Croker, Mark A. Atkinson, C. Craig Tisher, Richard J. Johnson
Journal: Journal of the American Society of Nephrology (2006)

The role of VEGF in vascular disease is complicated. Vascular endothelial growth factor (VEGF) expression can be deleterious in diabetic vasculopathy, especially in kidney and retina. In contrast, VEGF seems to be renoprotective in nondiabetic renal disease. VEGF exerts it biologic effects in association with nitric oxide (NO), yet it is known that NO bioavailability is reduced in diabetes. Thus, it was hypothesized that this diverse biologic effect of VEGF on diabetic vasculopathy is due to uncoupling of VEGF with NO. VEGF stimulated NO production in a dose-dependent manner in bovine aortic endothelial cells (BAEC), and this was inhibited by either high glucose or Nω-nitro-l-arginine methyl ester (L-NAME) treatment. Endothelial NO synthase phosphorylation by VEGF was also inhibited by high glucose. It is interesting that both high glucose and L-NAME enhanced the proliferative response of endothelial cells, which was prevented by an NO donor. Furthermore, high glucose as well as L-NAME stimulated VEGF and kinase-insert domain receptor (KDR) (VEGF receptor 2) mRNA expression in BAEC. These data suggest that the uncoupling of VEGF with NO enhances endothelial cell proliferation via the KDR pathway. Compatible with these findings, a KDR antagonist blocked this response. In addition, a VEGF mutant, which binds only KDR, induced extracellular signal–regulated kinase (ERK) activation, and inhibition of ERK completely blocked endothelial cell proliferation under this condition, suggesting a role of the KDR–ERK1/2 pathway on endothelial cell proliferation. In conclusion, high glucose causes an uncoupling of VEGF with NO, which enhances endothelial cell proliferation via activation of the KDR–ERK1/2 pathway. These results may provide new insights into the understanding of the mechanism of diabetic vascular disease.
Propagation through electrically coupled cells. Effects of regional changes in membrane properties.
Authors: R W Joyner, J Picone, R Veenstra, D Rawling
Journal: Circulation Research (1983)

The normal process of excitation of the heart involves propagation of action potentials through cardiac regions of different anatomy and different intrinsic membrane properties. Although our understanding of these properties is still incomplete, it is well accepted that the parameters measured from a single cell penetration in an electrical syncytium (e.g., action potential duration, rate of rise, and velocity) reflect not only the properties of that cell but also the electrotonic interactions with other cells to which the recorded cell is electrically coupled. We have used simulation techniques to predict the spatial distribution of action potential parameters resulting from discretely localized alterations in the intrinsic membrane properties of some of the cells of an electrical syncytium. We have shown that the resulting spatial distribution is markedly different for alterations in plateau and pacemaker currents vs. rising phase currents, and that other factors, such as the site of stimulation and the underlying spatial pattern of cell-cell coupling resistance, also modify the spatial distribution of action potential properties resulting from a discrete regional change in intrinsic membrane properties.
Extraordinary intrathecal bone reaction in β-thalassaemia intermedia
Authors: E Parano, V Pavone, F Di Gregorio, P Pavone, RR Trifiletti
Journal: The Lancet (1999)

We report on a patient with thalassaemia which was refractory to blood transfusions. The clinical picture was striking, and highlights the potential severity of intrathecal bone reactions after chronic intractable haemolytic anaemia.
Markers of Vascular Perturbation Correlate with Airway Structural Change in Asthma
Authors: Mats W. Johansson, Stanley J. Kruger, Mark L. Schiebler, Michael D. Evans, Ronald L. Sorkness, Loren C. Denlinger, William W. Busse, Nizar N. Jarjour, Robert R. Montgomery, Deane F. Mosher, Sean B. Fain
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Air trapping and ventilation defects on imaging are characteristics of asthma. Airway wall thickening occurs in asthma and is associated with increased bronchial vascularity and vascular permeability. Vascular endothelial cell products have not been explored as a surrogate to mark structural airway changes in asthma.Objectives: Determine whether reporters of vascular endothelial cell perturbation correlate with airway imaging metrics in patients with asthma of varying severity.Methods: Plasma from Severe Asthma Research Program subjects was analyzed by ELISAs for soluble von Willebrand factor mature protein (VWF:Ag) and propeptide (VWFpp), P-selectin, and platelet factor 4. Additional subjects were analyzed over 48 hours after whole-lung antigen challenge. We calculated ventilation defect volume by hyperpolarized helium-3 magnetic resonance imaging and areas of low signal density by multidetector computed tomography (less than −856 Hounsfield units [HU] at functional residual capacity and −950 HU at total lung capacity [TLC]).Measurements and Main Results: VWFpp and VWFpp/Ag ratio correlated with and predicted greater percentage defect volume on hyperpolarized helium-3 magnetic resonance imaging. P-selectin correlated with and predicted greater area of low density on chest multidetector computed tomography less than −950 HU at TLC. Platelet factor 4 did not correlate. Following whole-lung antigen challenge, variation in VWFpp, VWFpp/Ag, and P-selectin among time-points was less than that among subjects, indicating stability and repeatability of the measurements.Conclusions: Plasma VWFpp and P-selectin may be useful as surrogates of functional and structural defects that are evident on imaging. The results raise important questions about why VWFpp and P-selectin are associated specifically with different imaging abnormalities.
Maintenance Fluconazole Therapy for Recurrent Vulvovaginal Candidiasis
Authors: Jack D. Sobel, Harold C. Wiesenfeld, Mark Martens, Penny Danna, Thomas M. Hooton, Anne Rompalo, Malcolm Sperling, Charles Livengood, Benson Horowitz, James Von Thron, Libby Edwards, Helene Panzer, Teng-Chiao Chu
Journal: New England Journal of Medicine (2004)

No safe and convenient regimen has proved to be effective for the management of recurrent vulvovaginal candidiasis.
Acute respiratory acidosis decreases left ventricular contractility but increases cardiac output in dogs.
Authors: K R Walley, T H Lewis, L D Wood
Journal: Circulation Research (1990)

To understand the cardiovascular response to respiratory acidosis, we measured hemodynamics, left ventricular pressure, and left ventricular volume (three ultrasonic crystal pairs) during eucapnia and respiratory acidosis in 10 fentanyl-anesthetized open-chest dogs. Left ventricular contractility was assessed primarily by measuring the slope (Emax) and intercept (V0) of the left ventricular end-systolic pressure-volume relation determined by combining end-systolic points from a vena caval occlusion and from brief aortic cross-clamping. Respiratory acidosis (pH 7.09, Pco2 92 mm Hg) reduced contractility by a decrease in Emax (11.4 to 9.2 mm Hg/ml, p less than 0.01) with no change in V0. Despite this, cardiac output increased (1.7 to 2.1 l/min, p less than 0.01), and heart rate increased (96 to 121 beats/min, p less than 0.05), with no change in blood pressure. Systemic vascular resistance fell by 26% (p less than 0.01). During eucapnia, propranolol reduced Emax (11.4 to 4.6 mm Hg/ml, p less than 0.01) with no change in V0. After propranolol treatment, respiratory acidosis further reduced Emax (4.6 to 3.6 mm Hg/ml, p less than 0.05) and increased end-systolic volume more than before propranolol (p less than 0.001). Now cardiac output did not increase even though heart rate increased (81 to 106 beats/min, p less than 0.001) and systemic vascular resistance fell by 20% (p less than 0.01). We conclude that the effect of respiratory acidosis on the circulation is to increase venous return (equals cardiac output) in the face of decreased left ventricular contractility. The beta-adrenergic response to respiratory acidosis substantially ameliorated the increase in end-systolic volume and supported the increase in venous return but did not alter the associated tachycardia or vasodilation. Respiratory acidosis, like propranolol treatment, decreases contractility by decreasing Emax.
Rhinovirus aetiology at the first wheeze predict atopic but not non-atopic asthma at 7 years
Authors: Minna Lukkarinen, Tytti Vuorinen, Pasi Lehtinen, Olli Ruuskanen, Tuomas Jartti
Journal: European Respiratory Journal (2014)

Background:  Risk factors for childhood asthma have not been stratified according to asthma phenotype.   Objectives:  To investigate risk factors at the first wheeze for current atopic and non-atopic asthma at age 7 years.   Methods:  A cohort of 64 children hospitalized for their first wheezy episode was followed-up for 7 years. The primary outcomes were current atopic and non-atopic asthma at age 7 years. Risk factors were analyzed  post hoc , including sensitization (allergen specific IgE > 0.35 kU/l for common allergens), comprehensive viral aetiology and other known asthma risk factors. Logistic regression was used in statistics.   Results:  At study entry, the median age of the subjects was 12 months (range 3-35), 16% were sensitized and 92% were virus-positive. The overall univariable risk factors for current asthma at age 7 years were allergic rhinitis by 7 yrs (odds ratio 4.7; 95% CI 1.1-19; P = .033) and sensitization at study entry (5.0; 0.97-26; P = .054, respectively). The univariable risk factors for current atopic asthma (n=11) included rhinovirus aetiology (7.4; 1.7-32; P = .007) and sensitization at study entry(68; 9.8-472; P    Conclusions:  Our data suggest that rhinovirus etiology of the first wheeze in hospitalized children is a significant risk factor for current atopic but not non-atopic asthma at age 7 years. (ClinicalTrials.gov number, NCT 00494624).
Challenged by Complexity: My Twentieth Century in Immunology
Authors: Peter C. Doherty
Journal: Annual Review of Immunology (2006)

My research career has focused on complex experimental systems, principally virus-induced infectious processes. I have always run my own experimental program and never had a major mentor, although I have had many great colleagues. After graduating from the School of Veterinary Science at the University of Queensland, Australia, I worked for nine years on diseases of domestic animals. During that interval I completed a part-time PhD at the University of Edinburgh while employed as an experimental neuropathologist. Returning to the John Curtin School of Medical Research in Canberra, I focused on cell-mediated immunity, started to work seriously with mice, and thus became both an immunologist and a basic medical scientist. It was there in 1973 that Rolf Zinkernagel and I discovered MHC I–restricted CD8 + T cell recognition, a finding that, together with the “single T cell receptor/altered self” hypothesis that we developed to explain our results, led to the 1996 Nobel Prize for Physiology or Medicine. Part of my focus since then has been to communicate the societal value and power of science to the broader community. As my scientific life is not yet over, I confine the present historical account to the twentieth century.
Mechanism of Inhibition of Proximal Tubule Fluid Reabsorption after Exposure of the Rat Kidney to the Physical Effects of Expansion of Extracellular Fluid Volume
Authors: Iekuni Ichikawa, Barry M. Brenner
Journal: Journal of Clinical Investigation (1979)

The natriuresis and concomitant decline in absolute proximal reabsorption (APR) that occur in rats in response to saline loading are blunted markedly when renal perfusion pressure is reduced immediately before, but not after, the volume load. To ascertain the mechanism responsible for these differences between early clamp (EC) vs. late clamp (LC), intracapillary and interstitial determinants of peritubular capillary uptake of APR were measured in seven LC and seven EC Munich-Wistar rats before and after isotonic saline loading (80% body wt). With volume expansion in LC animals, we observed a marked decline in APR (averaging 11±1 nl/min), associated with large increases in urinary sodium excretion rate, which averaged 8±2 μeq/min. In EC, the changes in urinary sodium excretion rate (+1±0 μeq/min) and APR (−3±1 nl/min) with volume expansion were smaller in magnitude. Since peritubular capillary reabsorption coefficient and mean peritubular transcapillary hydraulic pressure difference did not change with saline loading in LC, the marked fall in APR was attributed primarily to a measured large decline in mean peritubular transcapillary oncotic pressure difference (δ̄π̄). Despite an equivalent mean fall in δ̄π̄ with volume expansion in EC, near-constancy of APR was found to be associated with a simultaneous and equivalent decline in mean peritubular transcapillary hydraulic pressure difference (a consequence of decreased mean peritubular capillary hydraulic pressure), which effectively offset the fall in δ̄π̄. These results demonstrate the importance of hydraulic pressure patterns of the peritubular capillaries in modulating APR and are consistent with the view that Starling forces across the postglomerular microcirculation play a fundamental role in determining APR.
Small intestinal stricture complicating superior mesenteric vein thrombosis. A study of three cases.
Authors: C Eugene, D Valla, L Wesenfelder, A Fingerhut, A Bergue, J Merrer, C Felsenheld, A Moundji, J C Etienne
Journal: Gut (1995)

Mesenteric vein thrombosis associated with intestinal stricture, as a consequence of intestinal ischaemia, has only been mentioned twice in published works. The clinical, biological, and morphological aspects as well as the treatment of this morbid association were studied in three patients. In all, a two stage clinical course (initial acute abdominal pain and fever, followed by chronic intestinal obstruction), corresponding to the sequence thrombosis/stricture, was found. x Ray studies showed a regularly contoured intestinal stricture. Surgical resection was required in all three cases for stricture, associated in one case with mesenteric infarction. Anticoagulation treatment was used to preclude recurrence. Increased clinical awareness could lead to the diagnosis of intestinal stricture secondary to mesenteric vein thrombosis more often and at an earlier stage. Treatment consists of evaluation of predisposing features, intestinal resection when necessary, and anticoagulation therapy, as indicated.
Diagnosis and Treatment of Osteoporosis
Authors: B H Mitlak, S R Nussbaum
Journal: Annual Review of Medicine (1993)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Genetic interactions in the spontaneous production of endogenous murine leukemia virus in low leukemic mouse strains.
Authors: J McCubrey, R Risser
Journal: The Journal of Experimental Medicine (1982)

The spontaneous expression of ecotropic murine leukemia virus (MuLV) in spleen cells of BALB/c, C57BL/6 (B6), and derivative mice was examined as a function of age. The patterns of spontaneous virus induction in vivo correlate with the patterns of virus induction in vitro, which result from the action of two loci, Inc-l and Inb-l (7). Whereas mice carrying Inc-l or Inb-l have similar phenotypes in vitro, they have significantly different phenotypes in vivo. Mice of the Inb-l+/+ genotype, e.g., B6, rarely expressed MuLV, and the titer of MuLV recovered from rare MuLV-positive mice of this genotype was usually low. Mice of the Inc-l+/+ genotype, e.g., BALB/c, expressed low amounts of MuLV early in life, however, from 6-12 mo of age approximately one-half of the Inc-l+/+ mice expressed virus, frequently of high titer. Equal numbers of N-tropic and B-tropic MuLV were recovered from Inb-l+ mice, but predominantly N-tropic MuLV was recovered from Inc-l+ mice. Strains that carry dominant (+) alleles at both Inc-l and Inb-l show higher titers of MuLV earlier in life than strains that carry only Inc-l or Inb-l. The presence of dominant alleles at both loci results in the appearance of predominantly N-tropic virus early in life. These results demonstrate that the principal determinants of spontaneous virus expression in these low leukemic strains of mice are the In loci or genes linked to them. A further inference that can be drawn from these studies is that the appearance of B-tropic virus is by no means a random process but rather results from predictable patterns of MuLV expression and alteration.
Cefixime Allows Greater Dose Escalation of Oral Irinotecan: A Phase I Study in Pediatric Patients With Refractory Solid Tumors
Authors: Wayne L. Furman, Kristine R. Crews, Catherine Billups, Jianrong Wu, Amar J. Gajjar, Najat C. Daw, Christian C. Patrick, Carlos Rodriguez-Galindo, Clinton F. Stewart, Jeffrey S. Dome, John C. Panetta, Peter J. Houghton, Victor M. Santana
Journal: Journal of Clinical Oncology (2006)

Purpose Irinotecan is active against a variety of malignancies; however, severe diarrhea limits its usefulness. In our phase I study, the intravenous formulation of irinotecan was administered orally daily for 5 days for 2 consecutive weeks (repeated every 21 days) to children with refractory solid tumors. Our objectives were to determine the maximum-tolerated dose (MTD), dose-limiting toxicity, and pharmacokinetics of oral irinotecan and to evaluate whether coadministration of cefixime (8 mg/kg/d beginning 5 days before irinotecan and continuing throughout the course) ameliorates irinotecan-induced diarrhea. Patients and Methods In separate cohorts, irinotecan doses were escalated from 15 to 45 mg/m 2 /d without cefixime and then from 45 to 60 and 75 mg/m 2 /d with cefixime. Results Without cefixime, diarrhea was dose limiting at irinotecan 45 mg/m 2 /d. Myelotoxicity was not significant at any dose. The MTD was 40 mg/m 2 /d without cefixime but 60 mg/m 2 /d with cefixime. Systemic exposure to SN-38 at the MTD was significantly higher with cefixime than without cefixime (mean SN-38 area under the curve: 19.5 ng×h/mL; standard deviation [SD], 6.8 ng × h/mL v 10.4 ng × h/mL; SD, 4.3 ng × h/mL, respectively; P = .030). Conclusion Cefixime administered with oral irinotecan is well tolerated in children and allows greater dose escalation of irinotecan. Because diarrhea is a major adverse effect of both intravenous and oral irinotecan, further evaluation of the use of cefixime to ameliorate this adverse effect is warranted.