tbuckley/cabot-search huggingface dataset:
Origin of nitrite and nitrate in nasal and exhaled breath condensate and relation to nitric oxide formation
Authors: H Marteus
Journal: Thorax (2005)

<b>Background:</b> Raised concentrations of nitrate and nitrite have been found in exhaled breath condensate (EBC) in airway disease, and it has been postulated that this reflects increased nitric oxide (NO) metabolism. However, the chemical and anatomical origin of nitrate and nitrite in the airways has not yet been sufficiently studied. <b>Methods:</b> The fraction of exhaled NO at an exhalation flow rate of 50 ml/s (FE<sub>NO</sub>) and nitrite and nitrate in EBC, nasal condensate, and saliva were measured in 17 tracheostomised and 15 non-tracheostomised subjects, all of whom were non-smokers without respiratory disease. Tracheal and oral samples were taken from the tracheostomised subjects and nasal (during velum closure) and oral samples from the non-tracheostomised subjects. Measurements were performed before and after sodium nitrate ingestion (10 mg/kg) and use of antibacterial mouthwash (chlorhexidine 0.2%). <b>Results:</b> In tracheostomised subjects oral FE<sub>NO</sub> increased by 90% (p&lt;0.01) while tracheal FE<sub>NO</sub> was not affected 60 minutes after nitrate ingestion. Oral EBC nitrite levels were increased 23-fold at 60 minutes (p&lt;0.001) whereas the nitrite levels in tracheal EBC showed only a minor increase (fourfold, p&lt;0.05). Nitrate was increased the same amount in oral and tracheal EBC at 60 minutes (2.5-fold, p&lt;0.05). In non-tracheostomised subjects oral FE<sub>NO</sub> and EBC nitrite increased after nitrate ingestion and after chlorhexidine mouthwash they approached baseline levels again (p&lt;0.001). Nasal NO, nitrate, and nitrite were not affected by nitrate intake or mouthwash. At baseline, mouthwash with deionised water did not affect nitrite in oral EBC or saliva, whereas significant reductions were seen after antibacterial mouthwash (p&lt;0.05 and p&lt;0.001, respectively). <b>Conclusions:</b> Besides the salivary glands, plasma nitrate is taken up by the lower airways but not the nasal airways. Nitrate levels in EBC are thus influenced by dietary intake. Nitrate is reduced to nitrite by bacterial activity which takes place primarily in the oropharyngeal tract of healthy subjects. Only oropharyngeal nitrite seems to contribute to exhaled NO in non-inflamed airways, and there is also a substantial contribution of nitrite from the oropharyngeal tract during standard collection of EBC.
Nitric Oxide Boosts Chemoimmunotherapy via Inhibition of Acid Sphingomyelinase in a Mouse Model of Melanoma
Authors: Cristiana Perrotta, Laura Bizzozero, Sestina Falcone, Patrizia Rovere-Querini, Alessandro Prinetti, Edward H. Schuchman, Sandro Sonnino, Angelo A. Manfredi, Emilio Clementi
Journal: Cancer Research (2007)

Abstract Cisplatin is one of the most effective anticancer drugs, but its severe toxic effects, including depletion of immune-competent cells, limit its efficacy. We combined the systemic treatment with cisplatin with intratumor delivery of dendritic cells (DC) previously treated ex vivo with a pulse of nitric oxide (NO) released by the NO donors (z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]-diazen-1-ium-1,2-diolate or isosorbide dinitrate. We found that this chemoimmunotherapy, tested in the B16 mouse model of melanoma, was significantly more efficacious than cisplatin alone, leading to tumor regression and animal survival at low doses of cisplatin that alone had no effect. Tumor cure was not observed when combining cisplatin with DCs not exposed to NO donors, indicating the key role of the pretreatment with NO. We investigated the mechanisms responsible for the synergic effect of NO-treated DCs and cisplatin and found that NO-treated DCs were protected both in vitro and in vivo from cisplatin-induced cytotoxicity. Cisplatin triggered DC apoptosis through increased expression and activation of acid sphingomyelinase; pretreatment of DCs with NO donors prevented such activation and inhibited activation of the downstream proapoptotic events, including generation of ceramide, activation of caspases 3 and 9, and mitochondrial depolarization. The effects of NO were mediated through generation of its physiologic messenger, cyclic GMP. We conclude that NO and NO generating drugs represent promising tools to increase the efficacy of chemoimmunotherapies in vivo, promoting the survival and increasing the function of injected cells by targeting a key pathway in cisplatin-induced cytotoxicity. [Cancer Res 2007;67(16):7559–64]
Behavioral Tolerance to Alcohol in Moderate Drinkers
Authors: DONALD W. GOODWIN, BARBARA POWELL, JOHN STERN
Journal: American Journal of Psychiatry (1971)

Alcohol was administered to young male volunteers with a history of light or moderate drinking. Subjects with the greatest drinking experience performed significantly better on a motor task and took fewer "risks" than did subjects with less drinking experience. Drinking history did not correlate with cognitive performance, indicating that tolerance to alcohol occurs in moderate drinkers but does not equally affect all types of functioning. Tolerance was not associated with an increased rate of alcohol metabolism.
INFLUENCE OF MYOCARDIAL ISCHEMIA ON OUTCOMES IN PATIENTS WITH SYSTOLIC VERSUS NON-SYSTOLIC HEART FAILURE
Authors: Thomas E. Vanhecke, Barry A. Franklin, Prem Soman, Avijit Lahiri, Jennifer H. Mieres, Tina Sias, Dennis Calnon, David Wolinsky, George Beller, Kenneth Burnham, Laurence Conway, Joseph Wight, Mary Walsh, Edouard Daher, Gary Heller, James E. Udelson, Peter A. McCullough
Journal: Journal of the American College of Cardiology (2011)
Chronic endurance exercise induces quadriceps nitrosative stress in patients with severe COPD
Authors: E Barreiro, R Rabinovich, J Marin-Corral, J A Barbera, J Gea, J Roca
Journal: Thorax (2008)

<h3>Background:</h3> Although exercise training has beneficial effects on skeletal muscle bioenergetics and exercise performance in patients with severe chronic obstructive pulmonary disease (COPD), it may also be associated with increased quadriceps oxidative and nitrosative stress. The aim of this study was to explore quadriceps oxidative and nitrosative stress in patients with severe COPD, both before and after a 3 week endurance exercise programme, and to identify the nature of the oxidatively modified proteins. <h3>Methods:</h3> Reactive carbonyls, hydroxynonenal–protein adducts, antioxidant enzymes, nitric oxide synthase (NOS) and 3-nitrotyrosine levels were determined in the quadriceps (pre- and post-exercise) of 15 patients with severe COPD and seven healthy controls using immunoblotting (one- and two-dimensional electrophoresis), activity assays and mass spectrometry. <h3>Results:</h3> At baseline, muscle levels of reactive carbonyls, which were negatively associated with muscle strength and exercise tolerance, were significantly higher in patients than in controls. Moreover, baseline hydroxynonenal–protein adducts, superoxide dismutase activity, inducible NOS and 3-nitrotyrosine immunoreactivity levels were also significantly increased in the quadriceps of patients compared with controls. In patients, chronic exercise induced a significant rise in inducible NOS levels and a fourfold increase in protein nitration. Chronic endurance exercise induced tyrosine nitration of muscle enolase 3β, aldolase A, triosephosphate isomerase, creatine kinase, carbonic anhydrase III, myoglobin and uracil DNA glycosylase in the quadriceps of patients, while contractile protein alpha-1 actin was nitrated only in patients exhibiting muscle loss (post hoc analysis). Superoxide dismutase activity increased after the exercise programme only in controls. <h3>Conclusions:</h3> In severe COPD, chronic endurance exercise induces increased tyrosine nitration of quadriceps proteins involved in glycolysis, energy distribution, carbon dioxide hydration, muscle oxygen transfer, DNA repair and contractile function in patients exhibiting systemic effects of the disease.
Pathological and Therapeutical Considerations Relative to Inflammation and Fever
Authors: C. H. Jones
Journal: BMJ (1859)

sional large draughts of warm water when the sickness seemed greatest, he recovered from that attack.The gall-stones, no doubt, passed successfully, which, from the presence of severe jaundice, is more probable than that they receded and returned into the bladder.In the following year, he had another and more severe attack.It is probable that in this attack the false passage was formed from the gall-bladder to the duodenum, which I dis- covered at the post mortem examination, and the cystic ter- mination of wlich enclosed an impacted calculus.The attack terminated witl the discharge of gall-stones, brown biliary matter, anid subsequent bilious diarrhoea.From that time he began to take the celebrated mixture of
Histone Acetylation and Recruitment of Serum Responsive Factor and CREB-Binding Protein Onto SM22 Promoter During SM22 Gene Expression
Authors: Ping Qiu, Li Li
Journal: Circulation Research (2002)

Chromatin acetylation and deacetylation catalyzed by histone acetyltransferases (HATs) and histone deacetylases (HDACs) are closely related to eukaryotic gene transcription. Although the binding of serum response factor (SRF) to the CArG boxes in the promoter region is necessary for SM22 expression, it has never been examined whether the local chromatin modification is involved in SM22 gene regulation. In this study, we used the SM22 gene as a model to address whether transcriptional activation of the gene can be manipulated through adjusting histone acetylation of the chromatin template and whether SRF- and HAT-containing coactivators can be recruited onto the SM22 promoter region during gene activation. Here, we showed that the stimulation of the SM22 promoter by the coactivator CREB-binding protein (CBP) was dependent on HAT activity. Overexpression of HDACs decreased SM22 promoter activity, whereas trichostatin A, an HDAC inhibitor, stimulated SM22 promoter activity in a CArG box-dependent manner and induced endogenous SM22 gene expression. Chromatin immunoprecipitation assays showed that trichostatin A treatment in 10T1/2 cells induces chromatin hyperacetylation in the SM22 gene. Although histone hyperacetylation of the SM22 gene occurred during SM22 gene expression and SRF and CBP immunocomplexes possess HAT activities in smooth muscle cells, both SRF and CBP were recruited to the CArG box-containing region of the promoter. This study provides evidence that chromatin acetylation is involved in smooth muscle cell-specific gene regulation.
Relationship of Birth Cohort and Early Age at Onset of Illness in a Bipolar Disorder Case Registry
Authors: K. N. Roy Chengappa, David J. Kupfer, Ellen Frank, Patricia R. Houck, Victoria J. Grochocinski, Patricia A. Cluss, Debra A. Stapf
Journal: American Journal of Psychiatry (2003)

Utilizing data from a previously characterized registry of subjects with bipolar illness, the authors examined age at onset of the first illness episode in cohorts of subjects born from 1900 through 1939 and from 1940 through 1959.Demographic and clinical characteristics at the first full episode of bipolar disorder of subjects in a diagnostically validated voluntary bipolar disorder registry (N=1,218) were reviewed and subjected to statistical analyses.The median age at onset of the first episode of bipolar illness was lower by 4.5 years in subjects born during or after 1940 (median age=19 years), compared with subjects born before 1940 (median age=23.5 years). The proportion of subjects with bipolar disorder presenting with a prepubertal onset was significantly higher in the later birth-year cohort than in the earlier birth-year cohort. More than 50% of male and female subjects in both cohorts had a depressive episode as the first episode of bipolar illness. Subjects in each cohort who had a parent with major depression, bipolar disorder, or schizophrenia experienced their first episode nearly 4 to 5 years earlier than the other subjects in the cohort.Prospective epidemiological studies conducted with bipolar disorder subjects are needed to either affirm or refute these data on age at illness onset. If the results are affirmed, the early recognition of prepubertal bipolar disorder will be important, so that the condition can be treated with appropriate medications and medications that could potentially worsen the illness course can be avoided. Similarly, early recognition of bipolar illness is important, especially in women, to minimize use of antidepressant monotherapy for patients with bipolar illness. Among young people presenting with major depression as the first illness episode, a parental history of major depression, bipolar disorder, or psychosis may be a useful pointer to future bipolar disorder. Early recognition and appropriate treatment of bipolar illness may prevent the development of chronicity and serious functional impairment.
Progression and Regression: Distinct Developmental Patterns of Diabetic Retinopathy in Patients With Type 2 Diabetes Treated in the Diabetes Care System West-Friesland, the Netherlands
Authors: Hata Zavrelova, Trynke Hoekstra, Marjan Alssema, Laura M.C. Welschen, Giel Nijpels, Annette C. Moll, Henrica C.W. de Vet, Bettine C.P. Polak, Jacqueline M. Dekker
Journal: Diabetes Care (2011)

OBJECTIVE To identify distinct developmental patterns of diabetic retinopathy (DR) and assess the risk factor levels of patients in these clusters. RESEARCH DESIGN AND METHODS A cohort of 3,343 patients with type 2 diabetes mellitus (T2DM) monitored and treated in the Diabetes Care System West-Friesland, the Netherlands, was followed from 2 to 6 years. Risk factors were measured, and two-field fundus photographs were taken annually and graded according to the EURODIAB study group. Latent class growth modeling was used to identify distinct developmental patterns of DR over time. RESULTS Five clusters of patients with distinct developmental patterns of DR were identified: A, patients without any signs of DR (88.9%); B, patients with a slow regression from minimal background to no DR (4.9%); C, patients with a slow progression from minimal background to moderate nonproliferative DR (4.0%); D, patients with a fast progression from minimal or moderate nonproliferative to (pre)proliferative or treated DR (1.4%); and E, patients with persistent proliferative DR (0.8%). Patients in clusters A and B were characterized by lower risk factor levels, such as diabetes duration, HbA1c, and systolic blood pressure compared with patients in progressive clusters (C–E). CONCLUSIONS Clusters of patients with T2DM with markedly different patterns of DR development were identified, including a cluster with regression of DR. These clusters enable a more detailed examination of the influence of various risk factors on DR.
Increased carotid artery intima-media thickness may be associated with stroke in primary antiphospholipid syndrome
Authors: G Medina
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To investigate the prevalence and clinical significance of carotid artery intima-media thickness (IMT) in patients with primary antiphospholipid syndrome (APS). <b>Methods:</b> 28 patients with primary APS with at least a five year follow up, and 28 healthy subjects, matched by age and sex, were included in the study. Colour Doppler with high resolution B mode carotid ultrasonography and spectral analysis were performed in patients and controls. Information on cardiovascular risk factors and the clinical course were collected. <b>Results:</b> The mean (SD) age of patients and controls (12 male, 16 female in each group) was 40 (8.5) years; the mean (SD) disease duration 7.7 (3) years. Carotid artery IMT was found in 23/28 patients (2.6 (1.14) mm) and 7/28 controls (1.2 (0.44)) (p=0.0001). A decrease in the lumen diameter was also found in 11/28 patients with primary APS without carotid atherosclerotic plaque, and 2/28 controls (p=0.004). Hyperlipidaemia, diabetes, smoking, obesity, and hypertension were not associated with carotid artery IMT. Patients with carotid artery IMT had arterial vascular disease more often than patients without: 9/23 <i>v</i> 0/5 (p&lt;0.009). These patients had stroke (seven patients), myocardial infarction (one), and mesenteric thrombosis (one). Subjects with IMT had a threefold higher risk for stroke than those without IMT (95% CI 0.78 to 14.3). <b>Conclusions:</b> Patients with primary APS have a high prevalence of carotid artery IMT and a decreased lumen diameter. IMT in primary APS may be associated with stroke. Patients with primary APS with IMT must be considered as carriers of atherosclerosis.
Analysis of chronic obstructive pulmonary disease exacerbations with the dual bronchodilator QVA149 compared with glycopyrronium and tiotropium (SPARK): a randomised, double-blind, parallel-group study
Authors: Jadwiga A Wedzicha, Marc Decramer, Joachim H Ficker, Dennis E Niewoehner, Thomas Sandström, Angel Fowler Taylor, Peter D'Andrea, Christie Arrasate, Hungta Chen, Donald Banerji
Journal: The Lancet Respiratory Medicine (2013)
Conventional Adjuvant Chemotherapy Versus Single-Cycle, Autograft-Supported, High-Dose, Late-Intensification Chemotherapy in High-Risk Breast Cancer Patients: A Randomized Trial
Authors: R. C. F. Leonard, M. Lind, C. Twelves, R. Coleman, S. van Belle, C. Wilson, J. Ledermann, I. Kennedy, P. Barrett-Lee, T. Perren, M. Verrill, D. Cameron, E. Foster, A. Yellowlees, J. Crown
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Breast cancer patients with four or more positive axillary lymph nodes who are treated with conventional adjuvant therapy have a poor prognosis. In uncontrolled studies, high-dose chemotherapy produced much better results than conventional therapy. We compared the benefits of a single cycle of high-dose chemotherapy and the benefits of conventional chemotherapy in patients with high-risk breast cancer in a prospective, unblinded, randomized trial. Methods: Between February 23, 1995, and June 29, 1999, 605 patients with breast cancer who had four or more positive lymph nodes were randomly assigned to treatment (307 to high-dose therapy and 298 to conventional therapy). The conventional chemotherapy regimen was four cycles of doxorubicin (75 mg/m 2 ) followed by eight cycles of CMF (cyclophosphamide [600 mg/m 2 ], methotrexate [50 mg/m 2 ], and 5-fluorouracil [600 mg/m 2 ]), all given intravenously on day 1 of a 21-day cycle. The high-dose regimen was four cycles of doxorubicin (75 mg/m 2 ), followed by a single cycle of intermediate-dose cyclophosphamide (4000 mg/m 2 ) supported by filgrastim (300 μg/day) for up to 10 days followed by high-dose cyclophosphamide (6000 mg/m 2 ) and thiotepa (800 mg/m 2 ). Peripheral blood progenitor cells were harvested by leukapheresis after treatment with cyclophosphamide and filgrastim and then re-infused after the high-dose cycle. Log-rank tests were used to compare survival rates. All statistical analyses were two-sided. Results: At a median follow-up of 6 years, no statistically significant differences were detected between the arms in 5-year relapse-free survival (high-dose arm = 57%, 95% confidence interval [CI] = 51% to 63%; conventional-dose arm = 54%, 95% CI = 48% to 61% ( P = .73) or in 5-year overall survival (high-dose arm = 62%, 95% CI = 56% to 68%; conventional-dose arm = 64%, 95% CI = 57% to 70%) ( P = .38). Conclusion: Autograft-supported, high-dose therapy is not superior to conventional chemotherapy in patients with breast cancer who have multiple involved lymph nodes. This conclusion should be viewed in the context of improving the success of conventional chemotherapy.
Evaluation of the safety and pharmacodynamics of Hematide, a novel erythropoietic agent, in a phase 1, double-blind, placebo-controlled, dose-escalation study in healthy volunteers
Authors: Richard B. Stead, John Lambert, Dawie Wessels, Julie S. Iwashita, Kerstin K. Leuther, Kathryn W. Woodburn, Peter J. Schatz, Douglas M. Okamoto, Robert Naso, Anne-Marie Duliege
Journal: Blood (2006)
Heart-lung interactions: applications in the critically ill
Authors: HE Fessler
Journal: European Respiratory Journal (1997)

Since the circulatory and pulmonary systems are both driven by pressure and share space in the thorax, it is inevitable that they interact. These mechanical interactions, whilst relatively few in number, are protean in their manifestations. The circulatory system of the critically ill is often particularly susceptible to interference from respiration. Compensatory reserve is limited, ventilatory effort increased, and many critical care respiratory interventions place strain on the circulation, not seen in health. This review will examine the basic physiological mechanisms through which the pulmonary and circulatory systems interact. These mechanisms will then be applied to a variety of weaning, positive end-expiratory pressure (PEEP), and cardiopulmonary resuscitation techniques. It is hoped that this will provide the tools to understand clinical observations which would otherwise appear inexplicable.
Subliminal Instrumental Conditioning Demonstrated in the Human Brain
Authors: Mathias Pessiglione, Predrag Petrovic, Jean Daunizeau, Stefano Palminteri, Raymond J. Dolan, Chris D. Frith
Journal: Neuron (2008)

How the brain uses success and failure to optimize future decisions is a long-standing question in neuroscience. One computational solution involves updating the values of context-action associations in proportion to a reward prediction error. Previous evidence suggests that such computations are expressed in the striatum and, as they are cognitively impenetrable, represent an unconscious learning mechanism. Here, we formally test this by studying instrumental conditioning in a situation where we masked contextual cues, such that they were not consciously perceived. Behavioral data showed that subjects nonetheless developed a significant propensity to choose cues associated with monetary rewards relative to punishments. Functional neuroimaging revealed that during conditioning cue values and prediction errors, generated from a computational model, both correlated with activity in ventral striatum. We conclude that, even without conscious processing of contextual cues, our brain can learn their reward value and use them to provide a bias on decision making.
Lansley denies competition will be fierce in NHS under reforms
Authors: A. O'Dowd
Journal: BMJ (2011)

The NHS will not be subjected to intense new competition among providers of services, health secretary Andrew Lansley has told MPs.

Mr Lansley, giving evidence to the parliamentary health select committee on 22 March as part of its final evidence session of an inquiry into commissioning, attempted to placate worries that fierce competition for competition’s sake would form part of his planned NHS reforms.

MPs asked about a potential conflict between the desire of GP commissioning consortiums to make decisions on spending for patient care and the insistence of the new economic regulator Monitor on competition between providers.

Mr Lansley said the Health and Social Care Bill was not introducing a radical new level of competition in the NHS.

“We are not changing the …
Conventional physiotherapy and forced expiration manoeuvres have similar effects on tracheobronchial clearance
Authors: M van Hengstum, J Festen, C Beurskens, M Hankel, F Beekman, F Corstens
Journal: European Respiratory Journal (1988)

This study compared the effect of two forms of chest physiotherapy. In the "conventional" form of physiotherapy, postural drainage was combined with percussion and directed coughing. The other, relatively new form of physiotherapy, was the forced expiration technique, i.e. huffing combined with postural drainage, breathing exercises and, if necessary, coughing. Eight patients (six with cystic fibrosis, two with agammaglobulinaemia) took part in the study. No difference was found in tracheobronchial clearance, regional lung clearance, sputum production or lung function between the two forms of treatment. The forced expiration technique can be performed without an assistant. Therefore, it is concluded that in general the forced expiration technique is preferable.