tbuckley/cabot-search huggingface dataset:
Impact of Generalized Social Anxiety Disorder in Managed Care
Authors: David J. Katzelnick, Kenneth A. Kobak, Thomas DeLeire, Henry J. Henk, John H. Greist, Jonathan R.T. Davidson, Franklin R. Schneier, Murray B. Stein, Cindy P. Helstad
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The authors determined the costs associated with generalized social anxiety disorder in a managed care setting. METHOD: A three-phase mail and telephone survey was conducted from July to October 1998 in two outpatient clinics of a large health maintenance organization (HMO). The survey assessed direct costs, indirect costs, health-related quality of life, and clinical severity associated with generalized social anxiety disorder, both alone and with comorbid psychopathology. RESULTS: The weighted prevalence rate of current generalized social anxiety disorder was 8.2%. In the past year, only 0.5% of subjects with generalized social anxiety disorder had been accurately diagnosed. Yet 44.1% had a mental health specialty visit or had been prescribed an antidepressant, and psychiatric comorbidity was found in 43.6%. Noncomorbid generalized social anxiety disorder was associated with significantly lower health-related quality of life, work productivity, and earnings and greater utilization of health services; generalized social anxiety disorder with comorbid psychopathology was even more disabling. Suicide was attempted by 21.9% of subjects with noncomorbid generalized social anxiety disorder. Persons with average-severity generalized social anxiety disorder had probabilities of graduating from college that were 10 percentage points lower, earned wages that were 10% lower, and had probabilities of holding a technical, professional, or managerial job that were 14 percentage points lower than the comparison group. CONCLUSIONS: In a community cohort of HMO members, generalized social anxiety disorder was rarely diagnosed or treated despite being highly prevalent and associated with significant direct and indirect costs, comorbid depression, and impairment.
Synthesis of a family of amphiphilic glycopolymers via controlled ring-opening polymerization of functionalized cyclic carbonates and their application in drug delivery
Authors: Fabian Suriano, Russell Pratt, Jeremy P.K. Tan, Nikken Wiradharma, Alshakim Nelson, Yi-Yan Yang, Philippe Dubois, James L. Hedrick
Journal: Biomaterials (2010)
Highlights in lung cancer
Authors: C. Brambilla, S. Spiro
Journal: European Respiratory Journal (2001)

Lung cancer is a leading cause of death and a major public health problem throughout the world. Although chest physicians supervise the care of most of these patients in many European countries, the number of papers on lung cancer published in the European Respiratory Journal ( ERJ ) does not reflect the magnitude or the importance of the disease. Thoracic oncologists, both clinicians and biologists, prefer to send what they consider their best work to more cancer-orientated journals even if the impact factor is no higher. If we consider that the respiratory physician has to divide his time and expertise between infectious, inflammatory, thromboembolic and environmental respiratory diseases, but actually devote most of his time to asthma, chronic obstructive pulmonary disease and lung cancer, it seems pretty obvious that he may not find the information he needs on lung cancer in the ERJ . This new series on lung cancer is an opportunity to provide an overview on controversial or “hot” topics in the field, and to raise the respiratory physician's curiosity in an area he should know more …
Pertussis toxin inhibition of chemotactic factor-induced calcium mobilization and function in human polymorphonuclear leukocytes.
Authors: D W Goldman, F H Chang, L A Gifford, E J Goetzl, H R Bourne
Journal: The Journal of Experimental Medicine (1985)

Chemotactic factors stimulate a rapid increase in the cytosolic concentration of intracellular calcium ions ([Ca2+]in) in human polymorphonuclear leukocytes (PMNL), which may be an event that is critical to the expression of chemotaxis and other PMNL functions. Treatment of PMNL with pertussis toxin catalyzes ADP-ribosylation of a protein similar or identical to the inhibiting regulatory protein of adenylate cyclase, Gi, and suppresses the increase in [Ca2+]in elicited by leukotriene B4(LTB4) and formyl-methionyl-leucyl-phenylalanine. Chemotactic migration and lysosomal enzyme release elicited by chemotactic factors were inhibited by pertussis toxin with a concentration-dependence similar to that for inhibition of the increase in [Ca2+]in, without an effect on lysosomal enzyme release induced by the ionophore A23187 and phorbol myristate acetate. Activated pertussis toxin catalyzed the [32P]ADP-ribosylation of a 41 kD protein in homogenates of PMNL. The extent of [32P]ADP-ribosylation of this protein was reduced 59% by pretreatment of intact PMNL with pertussis toxin. Pertussis toxin selectively decreased the number of high-affinity receptors for LTB4 on PMNL by 60% without altering the number or binding properties of the low-affinity subset of receptors. Pertussis toxin modification of a membrane protein of PMNL analogous to Gi thus simultaneously alters chemotactic receptors and attenuates the changes in cytosolic calcium concentration and PMNL function caused by chemotactic factors.
Novel Inhibitors of Fatty Acid Synthase with Anticancer Activity
Authors: Teresa Puig, Carlos Turrado, Bellinda Benhamú, Helena Aguilar, Joana Relat, Silvia Ortega-Gutiérrez, Gemma Casals, Pedro F. Marrero, Ander Urruticoechea, Diego Haro, María Luz López-Rodríguez, Ramon Colomer
Journal: Clinical Cancer Research (2009)

PURPOSE: Fatty acid synthase (FASN) is overexpressed in human breast carcinoma. The natural polyphenol (-)-epigallocatechin-3-gallate blocks in vitro FASN activity and leads to apoptosis in breast cancer cells without any effects on carnitine palmitoyltransferase-1 (CPT-1) activity, and in vivo, does not decrease body weight. We synthesized a panel of new polyphenolic compounds and tested their effects on breast cancer models. EXPERIMENTAL DESIGN: We evaluated the in vitro effects of the compounds on breast cancer cell growth (SK-Br3, MCF-7, and MDA-MB-231), apoptosis [as assessed by cleavage of poly(ADP-ribose) polymerase], cell signaling (HER2, ERK1/2, and AKT), and fatty acid metabolism enzymes (FASN and CPT-1). In vivo, we have evaluated their antitumor activity and their effect on body weight in a mice model of BT474 breast cancer cells. RESULTS: Two compounds potently inhibited FASN activity and showed high cytotoxicity. Moreover, the compounds induced apoptosis and caused a marked decrease in the active forms of HER2, AKT, and ERK1/2 proteins. Interestingly, the compounds did not stimulate CPT-1 activity in vitro. We show evidence that one of the FASN inhibitors blocked the growth of BT474 breast cancer xenografts and did not induce weight loss in vivo. CONCLUSIONS: The synthesized polyphenolic compounds represent a novel class of FASN inhibitors, with in vitro and in vivo anticancer activity, that do not exhibit cross-activation of beta-oxidation and do not induce weight loss in animals. One of the compounds blocked the growth of breast cancer xenografts. These FASN inhibitors may represent new agents for breast cancer treatment. (Clin Cancer Res 2009;15(24):7608-15).
Matrix metalloproteinase-9 deletion attenuates myocardial fibrosis and diastolic dysfunction in ageing mice
Authors: Ying Ann Chiao, Trevi A. Ramirez, Rogelio Zamilpa, S. Michelle Okoronkwo, Qiuxia Dai, Jianhua Zhang, Yu-Fang Jin, Merry L. Lindsey
Journal: Cardiovascular Research (2012)

AimsAge-related diastolic dysfunction has been attributed to an increased passive stiffness, which is regulated by extracellular matrix (ECM).We recently showed that matrix metalloproteinase (MMP)-9, an ECM mediator, increases in the left ventricle (LV) with age.The aim of this study, accordingly, was to determine the role of MMP-9 in cardiac ageing. Methods and resultsWe compared LV function in young (6-9 months), middle-aged (12 -15 months), old (18-24 months) and senescent (26-34 months) wild-type (WT) and MMP-9 null mice (n ≥ 12/group).All groups had similar fractional shortenings and aortic peak velocities, indicating that systolic function was not altered by ageing or MMP-9 deletion.The mitral ratios of early to late diastolic filling velocities were reduced in old and senescent WT compared with young controls, and this reduction was attenuated in MMP-9 null mice.Concomitantly, the increase in LV collagen content was reduced in MMP-9 null mice (n ¼ 5-6/group).To dissect the mechanisms of these changes, we evaluated the mRNA expression levels of 84 ECM and adhesion molecules by real-time qPCR (n ¼ 6/group).The expression of pro-fibrotic periostin and connective tissue growth factor (CTGF) increased with senescence, as did transforming growth factor-b (TGF-b)-induced protein levels and Smad signalling, and these increases were blunted by MMP-9 deletion.In senescence, MMP-9 deletion also resulted in a compensatory increase in MMP-8. ConclusionMMP-9 deletion attenuates the age-related decline in diastolic function, in part by reducing TGF-b signalling-induced periostin and CTGF expression and increasing MMP-8 expression to regulate myocardial collagen turnover and deposition.
Cardiovascular reflex modulation of plasma catecholamine concentrations in the anesthetized cat.
Authors: C M Heesch, V S Bishop
Journal: Circulation Research (1982)

The purpose of this study was to examine the role of carotid sinus and cardiopulmonary mechanoreceptors in the reflex control of adrenal medullary catecholamine secretion. Afferent input from carotid sinus and cardiopulmonary mechanoreceptors was decreased by carotid occlusion or cervical vagal cold block, respectively. Increases in arterial pressure were significantly greater when either intervention was tested in the presence of the other, with the role of the carotid sinus baroreflex being dominant. Neither carotid occlusion nor vagal cold block resulted in a significant increase in plasma epinephrine or norepinephrine concentrations. However, carotid occlusion during vagal block caused a significant increase in plasma epinephrine (+87%) and norepinephrine concentrations (+128%). Likewise, vagal block during carotid occlusion increased plasma epinephrine (+82%) and norepinephrine concentrations (+73%). Similar experiments performed in a group of chemically sympathectomized animals (pre-treated with 50 mg/kg 6-hydroxydopamine) indicted that adrenal medullary norepinephrine as well as epinephrine release could be modulated by the carotid sinus and cardiopulmonary reflexes. Mean arterial blood pressure and heart rate were significantly lower in 6-hydroxydopamine-treated animals, compared with untreated controls. Although of lesser magnitude, responses to carotid occlusion and vagal block in 6-hydroxydopamine-treated animals were qualitatively similar to those in untreated animals. Plasma catecholamine concentrations did not increase from either manipulation. However, when the second manipulation was added to the first, significant increases occurred. We conclude from these data that both the carotid sinus and cardiopulmonary reflexes modulate the release of adrenal catecholamines. An interaction between the two reflexes exists whereby the influence of one reflex on catecholamine secretion is apparent only in the absence of the other input.
High-intensity inspiratory muscle training in COPD
Authors: K. Hill, S. C. Jenkins, D. L. Philippe, N. Cecins, K. L. Shepherd, D. J. Green, D. R. Hillman, P. R. Eastwood
Journal: European Respiratory Journal (2006)

The aim of the present study was to investigate the effects of an interval-based high-intensity inspiratory muscle training (H-IMT) programme on inspiratory muscle function, exercise capacity, dyspnoea and health-related quality of life (QoL) in subjects with chronic obstructive pulmonary disease. A double-blind randomised controlled trial was performed. Sixteen subjects (11 males, mean forced expiratory volume in one second (FEV(1)) 37.4+/-12.5%) underwent H-IMT performed at the highest tolerable inspiratory threshold load (increasing to 101% of baseline maximum inspiratory pressure). Seventeen subjects (11 males, mean FEV(1 )36.5+/-11.5%) underwent sham inspiratory muscle training (S-IMT) at 10% of maximum inspiratory pressure. Training took place three times a week for 8 weeks and was fully supervised. Pre- and post-training measurements of lung function, maximum inspiratory pressure, maximum threshold pressure, exercise capacity, dyspnoea and QoL (Chronic Respiratory Disease Questionnaire; CRDQ) were obtained. H-IMT increased maximum inspiratory pressure by 29%, maximum threshold pressure by 56%, 6-min walk distance by 27 m, and improved dyspnoea and fatigue (CRDQ) by 1.4 and 0.9 points per item, respectively. These changes were significantly greater than any seen following S-IMT. In conclusion, high-intensity inspiratory muscle training improves inspiratory muscle function in subjects with moderate-to-severe chronic obstructive pulmonary disease, yielding meaningful reductions in dyspnoea and fatigue.
Effects of Exercise and Stress Management Training on Markers of Cardiovascular Risk in Patients With Ischemic Heart Disease
Authors: James A. Blumenthal, Andrew Sherwood, Michael A. Babyak, Lana L. Watkins, Robert Waugh, Anastasia Georgiades, Simon L. Bacon, Junichiro Hayano, R. Edward Coleman, Alan Hinderliter
Journal: JAMA (2005)

ContextObservational studies have shown that psychosocial factors are associated with increased risk for cardiovascular morbidity and mortality, but the effects of behavioral interventions on psychosocial and medical end points remain uncertain.ObjectiveTo determine the effect of 2 behavioral programs, aerobic exercise training and stress management training, with routine medical care on psychosocial functioning and markers of cardiovascular risk.Design, Setting, and PatientsRandomized controlled trial of 134 patients (92 male and 42 female; aged 40-84 years) with stable ischemic heart disease (IHD) and exercise-induced myocardial ischemia. Conducted from January 1999 to February 2003.InterventionsRoutine medical care (usual care); usual care plus supervised aerobic exercise training for 35 minutes 3 times per week for 16 weeks; usual care plus weekly 1.5-hour stress management training for 16 weeks.Main Outcome MeasuresSelf-reported measures of general distress (General Health Questionnaire [GHQ]) and depression (Beck Depression Inventory [BDI]); left ventricular ejection fraction (LVEF) and wall motion abnormalities (WMA); flow-mediated dilation; and cardiac autonomic control (heart rate variability during deep breathing and baroreflex sensitivity).ResultsPatients in the exercise and stress management groups had lower mean (SE) BDI scores (exercise: 8.2 [0.6]; stress management: 8.2 [0.6]) vs usual care (10.1 [0.6]; P = .02); reduced distress by GHQ scores (exercise: 56.3 [0.9]; stress management: 56.8 [0.9]) vs usual care (53.6 [0.9]; P = .02); and smaller reductions in LVEF during mental stress testing (exercise: −0.54% [0.44%]; stress management: −0.34% [0.45%]) vs usual care (−1.69% [0.46%]; P = .03). Exercise and stress management were associated with lower mean (SE) WMA rating scores (exercise: 0.20 [0.07]; stress management: 0.10 [0.07]) in a subset of patients with significant stress-induced WMA at baseline vs usual care (0.36 [0.07]; P = .02). Patients in the exercise and stress management groups had greater mean (SE) improvements in flow-mediated dilation (exercise: mean [SD], 5.6% [0.45%]; stress management: 5.2% [0.47%]) vs usual care patients (4.1% [0.48%]; P = .03). In a subgroup, those receiving stress management showed improved mean (SE) baroreflex sensitivity (8.2 [0.8] ms/mm Hg) vs usual care (5.1 [0.9] ms/mm Hg; P = .02) and significant increases in heart rate variability (193.7 [19.6] ms) vs usual care (132.1 [21.5] ms; P = .04).ConclusionFor patients with stable IHD, exercise and stress management training reduced emotional distress and improved markers of cardiovascular risk more than usual medical care alone.
Heterogeneity of asthma according to blood inflammatory patterns
Authors: R Nadif, V Siroux, M-P Oryszczyn, C Ravault, C Pison, I Pin, F Kauffmann
Journal: Thorax (2009)

<h3>Rationale:</h3> There is increasing interest regarding asthma heterogeneity in relation to inflammatory patterns. <h3>Objectives:</h3> To assess phenotypic characteristics, in particular clinical presentation of the disease, in 381 well-characterised adults with asthma from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) according to their blood inflammatory pattern. <h3>Methods:</h3> Four blood inflammatory patterns were defined according to eosinophil (EOS) and neutrophil (NEU) count cut-off points. Samples with ⩾250 EOS/mm<sup>3</sup> were classified as EOS<sup>hi</sup> and those with ⩾5000 NEU/mm<sup>3</sup> as NEU<sup>hi</sup>. Clinical characteristics include typical asthma and chronic obstructive pulmonary disease (COPD)-like symptoms, as well as composite quantitative scores addressing the activity of the disease. <h3>Results:</h3> A substantial number of those with asthma (56.2%) had the EOS<sup>lo</sup> pattern (&lt;250 EOS/mm<sup>3</sup>). Patients with asthma who had the EOS<sup>hi</sup> pattern had higher immunoglobulin E (IgE), a lower forced expiratory volume in 1 s (FEV<sub>1</sub>) and presented a more active asthma than those with the EOS<sup>lo</sup> pattern. Among those with the EOS<sup>lo</sup> pattern, neutrophil inflammation (NEU<sup>hi</sup>) was related to a less frequent positive skin prick test response (OR 0.44, 95% CI 0.20 to 0.96). Among those with the EOS<sup>hi</sup> pattern, neutrophil inflammation did not explain current asthma or asthma activity, and was significantly related to nocturnal symptoms (OR 5.21, 95% CI 1.44 to 18.8) independently of age, sex, smoking and inhaled corticosteroid treatment. In non-smokers with asthma, COPD-like symptoms, in particular chronic phlegm, were more frequent in those with neutrophil inflammation, independent of eosinophil inflammation (OR 2.35, 95% CI 1.08 to 5.10). <h3>Conclusions:</h3> Besides eosinophilia, neutrophil inflammation assessed in the blood is related to specific characteristics of asthma. Considering simultaneously neutrophilic and eosinophilic inflammation may contribute to help to disentangle this complex disease.
Delayed administration of dexrazoxane provides cardioprotection for patients with advanced breast cancer treated with doxorubicin-containing therapy.
Authors: S M Swain, F S Whaley, M C Gerber, M S Ewer, J R Bianchine, R A Gams
Journal: Journal of Clinical Oncology (1997)

PURPOSE To assess whether dexrazoxane (DZR) given after a cumulative doxorubicin dose of 300 mg/m2 confers cardioprotection in patients with advanced breast cancer treated with fluorouracil, doxorubicin, and cyclophosphamide (FAC). PATIENTS AND METHODS In two multicenter studies (088001 and 088006), patients were randomized to receive FAC and placebo (PLA) versus FAC and DZR. After a protocol amendment, all patients received open-label DZR after they had reached a cumulative doxorubicin dose of 300 mg/m2. Two groups were compared: 99 patients randomized to the PLA arms before the amendment who received FAC and PLA for at least seven courses (PLA group), and 102 patients randomized to the PLA arms after the amendment who received FAC and PLA for six courses followed by open-label DZR (PLA/DZR group). RESULTS The hazards ratio of PLA to PLA/DZR was 3.5 (95% confidence interval [CI], 2.2 to 5.7; P &lt; .001, logrank and generalized Wilcoxon tests) for the doxorubicin dose at any cardiac event, ejection fraction changes, or congestive heart failure (CHF). The hazards ratio of PLA to PLA/DZR was 13.1 (95% CI, 3.7 to 46.0; P &lt; .001, logrank and generalized Wilcoxon tests) for the doxorubicin dose at the development of CHF. The overall incidence of CHF in the PLA/DZR group was 3%, compared with 22% in the PLA group (P &lt; .001, Fisher's exact test). Twenty-six percent of PLA/DZR patients received at least 15 courses of therapy, compared with 5% of patients in the PLA group. These results do not appear to be attributable to a time trend. CONCLUSION DZR is a highly effective cardioprotective agent when used in patients with advanced breast cancer who continue to receive doxorubicin-based chemotherapy after a cumulative doxorubicin dose of 300 mg/m2 has been reached.
Ability of the Ischaemic Myocardium to Absorb Blood Perfused Artificially through a Previously Implanted Artery
Authors: P. C. Petropoulos
Journal: Thorax (1963)

Blood absorption from intramyocardially implanted arteries hasbeenevaluated bothexperimentally andclinically (Vineberg andJewett, 1947;GlennandBeal, 1950;Bencosme andVineberg, 1953;Bakst, Maniglia, Adam,andBailey, 1955;Sabiston, Fauteux, andBlalock, 1957; HaegerandWallgren, 1959a, b;andLopez-Belio, Rodriguez, Stansel, Tasaki, Gomez-Ferrer, and Julian, 1961). Middlecalibre arteries, suchasthe carotid orsubclavian, havebeenimplanted into themyocardium, notonlywiththeir endsopen butevenwithsideholes intheembedded portion, without theformation ofa haematoma. Such implanted arteries havebeenfoundtostaypatent, usually forfourtosixweeks. Somesuchimplantations haveremained patent forupto246days, thoughsimilar arterial implants intoskeletal muscle orother organs, suchasliver andspleen, produce early haematomas withresulting obliterationofthelumenoftheimplanted arteries (Sabiston etal.,1957). HaegerandWallgren (1959b) proved thatplastic tubes transplanted into themyocardium, bridging theinternal mammary artery andtheleft ventricular wall, could bekept patent forabout sixweeks, which waslongenough tosupply themyocardium withoxygenated blood duringthecritical phaseofligation ofthe coronary artery. Whensimilar shunts withtubes wereusedinthesamemannerinvarious organs, suchastheliver, spleen, andmuscles, theybecame obstructed after twotofivedays. Direct grafting ofa homologous vessel or a prosthetic device fromtheaortatothemyocardium hasbeen experimentally and clinically applied (Smith, Beasley, Hodes,Hall,Biel, andHuth,1957; HaegerandWallgren, 1959b). ISupported by grantsfromtheAmericanHeartAssociation and
A modeling framework for estimating children's residential exposure and dose to chlorpyrifos via dermal residue contact and nondietary ingestion.
Authors: V G Zartarian, H Ozkaynak, J M Burke, M J Zufall, M L Rigas, E J Furtaw
Journal: Environmental Health Perspectives (2000)

To help address the Food Quality Protection Act of 1996, a physically based probabilistic model has been developed to quantify and analyze dermal and nondietary ingestion exposure and dose to pesticides. The Residential Stochastic Human Exposure and Dose Simulation Model for Pesticides (Residential-SHEDS) simulates the exposures and doses of children contacting residues on surfaces in treated residences and on turf in treated residential yards. The simulations combine sequential time-location-activity information from children's diaries with microlevel videotaped activity data, probability distributions of measured surface residues and exposure factors, and pharmacokinetic rate constants. Model outputs include individual profiles and population statistics for daily dermal loading, mass in the blood compartment, ingested residue via nondietary objects, and mass of eliminated metabolite, as well as contributions from various routes, pathways, and media. To illustrate the capabilities of the model framework, we applied Residential-SHEDS to estimate children's residential exposure and dose to chlorpyrifos for 12 exposure scenarios: 2 age groups (0-4 and 5-9 years); 2 indoor pesticide application methods (broadcast and crack and crevice); and 3 postindoor application time periods (< 1, 1-7, and 8-30 days). Independent residential turf applications (liquid or granular) were included in each of these scenarios. Despite the current data limitations and model assumptions, the case study predicts exposure and dose estimates that compare well to measurements in the published literature, and provides insights to the relative importance of exposure scenarios and pathways.