tbuckley/cabot-search huggingface dataset:
Randomised placebo controlled trial of beta agonist dose reduction in asthma
Authors: T W Harrison, J Oborne, P J Wilding, A E Tattersfield
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Many patients continue to take regular β agonists, often at high doses, contrary to national and international guidelines. Some studies have suggested that this can worsen asthma control, but whether such patients can reduce their dose of β agonist and whether they would benefit from this has not been determined. Reduction of β agonist dose was studied in a placebo controlled parallel group study. <h3>METHODS</h3> Following a run in period, 33 subjects with asthma taking regular β agonists were converted to an equivalent dose of terbutaline via a Turbohaler. Two weeks later terbutaline was continued at the same dose or changed to placebo in two stages a week apart. The change over period was covered by an increased dose of inhaled steroid to attenuate any immediate effects of the change in dose. Subjects then attended weekly for six weeks for measurement of forced expiratory volume in one second (FEV<sub>1</sub>) and the dose of methacholine that produced a 20% fall in FEV<sub>1</sub> (PD<sub>20</sub>). Peak expiratory flow (PEF) and symptom scores were recorded twice daily throughout the study. Exacerbations, lung function, bronchial responsiveness, bronchodilator response, β agonist use, and symptoms were compared before and six weeks after reduction in the dose of β agonist. <h3>RESULTS</h3> Twenty five of the 33 subjects completed the study; three patients in each group withdrew due to an asthma exacerbation. The median terbutaline dose fell from 2500 to 500 μg/day in the β agonist reduction group and from 3000 to 2250 μg/day in the control group. There were small non-significant changes in FEV<sub>1</sub>, PEF, symptom scores and PD<sub>20</sub> methacholine over the course of the study. The FEV<sub>1</sub> response to a β agonist was greater in those who reduced their β agonist dose than in the control group although the final FEV<sub>1</sub> achieved was the same. <h3>CONCLUSIONS</h3> Patients with asthma taking high doses of β agonists can reduce the amount of β agonist they use without a significant change in their asthma control. There was no evidence of improved asthma control with β agonist dose reduction.
Eight year prognosis of postinfectious irritable bowel syndrome following waterborne bacterial dysentery
Authors: J. K. Marshall, M. Thabane, A. X. Garg, W. F. Clark, P. Moayyedi, S. M. Collins
Journal: Gut (2010)

<h3>Background</h3> Although postinfectious irritable bowel syndrome (PI-IBS) is a well-recognised complication of acute gastroenteritis, its prognosis remains poorly defined. The natural history of PI-IBS was assessed among participants in the Walkerton Health Study (WHS), which has followed the long-term effects of a large outbreak of acute gastroenteritis related to municipal water contamination in May 2000. <h3>Methods</h3> WHS participants were invited to return for annual assessment at a research clinic. Adult residents of Walkerton at the time of the outbreak who enrolled in 2002/2003 and returned for assessment in 2008 were eligible for a PI-IBS study cohort if they had no prior history of IBS or inflammatory bowel disease. A modified Bowel Disease Questionnaire was used to diagnose IBS by Rome I criteria and to identify IBS subtypes. <h3>Results</h3> Of 4561 WHS participants, 2451 returned for their 8 year assessment and 1166 were eligible for the PI-IBS study cohort (688 females, mean age 46.2 years). The prevalence of IBS among 742 eligible subjects who suffered acute gastroenteritis during the outbreak declined from 28.3% after 2–3 years to 15.4% after 8 years, but remained significantly increased compared with controls who did not have acute gastroenteritis (OR 3.12; 95% CI 1.99 to 5.04). Independent risk factors for PI-IBS at 8 years included female gender, younger age, prior anxiety/depression, and fever or weight loss during the acute enteric illness. IBS subtypes were not stable over time. <h3>Conclusions</h3> Acute gastroenteritis can trigger IBS symptoms that persist for at least 8 years. Characteristics of the host and the acute enteric illness can predict the long-term risk of PI-IBS.
Depressive Disorder and Incident Diabetes Mellitus: The Effect of Characteristics of Depression
Authors: Antonio Campayo, Peter de Jonge, Juan F Roy, Pedro Saz, Concepción de la Cámara, Miguel A. Quintanilla, Guillermo Marcos, Javier Santabárbara, Antonio Lobo
Journal: American Journal of Psychiatry (2010)

The purpose of this study was to test the hypothesis that clinically significant depression detected in a population sample increases the risk of diabetes mellitus. The authors examined the effect of characteristics of depression frequently found in the community on the risk of incident diabetes mellitus.A large community sample of adults aged > or = 55 years (N=4,803) was assessed at baseline in a longitudinal three-wave epidemiological enquiry using a psychiatric interview and the Geriatric Mental State Schedule. Cases of depression were diagnosed according to standardized criteria, and diabetes was assessed using a risk factors questionnaire. Follow-up evaluations, conducted 2.5 and 5 years later, were completed to determine the incidence of diabetes.At baseline, 379 case subjects with depression were identified. The risk of incident diabetes mellitus was higher among subjects with depression when compared with nondepressed subjects, and the association remained significant after controlling for potential confounders, including diabetes risk factors. The estimated rate of diabetes mellitus attributable to depression was 6.87%. An increased risk of diabetes mellitus was also associated with the following characteristics of depression: nonsevere depression, persistent depression, and untreated depression. Treatment with antidepressants was not associated with an increased risk of diabetes mellitus.Clinically significant depression is associated with a 65% increased risk of diabetes mellitus. Characteristics of depression frequently found in the community, namely nonsevere depression, persistent depression, and untreated depression, may play a role in the development of diabetes in a predominantly elderly adult population.
An Inflammatory Biomarker as a Differential Predictor of Outcome of Depression Treatment With Escitalopram and Nortriptyline
Authors: Rudolf Uher, Katherine E. Tansey, Tracy Dew, Wolfgang Maier, Ole Mors, Joanna Hauser, Mojca Zvezdana Dernovsek, Neven Henigsberg, Daniel Souery, Anne Farmer, Peter McGuffin
Journal: American Journal of Psychiatry (2014)

Objective: Major depressive disorder has been linked with inflammatory processes, but it is unclear whether individual differences in levels of inflammatory biomarkers could help match patients to treatments that are most likely to be beneficial. The authors tested the hypothesis that C-reactive protein (CRP), a commonly available marker of systemic inflammation, predicts differential response to escitalopram (a serotonin reuptake inhibitor) and nortriptyline (a norepinephrine reuptake inhibitor). Method: The hypothesis was tested in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study, a multicenter open-label randomized clinical trial. CRP was measured with a high-sensitivity method in serum samples from 241 adult men and women with major depressive disorder randomly allocated to 12-week treatment with escitalopram (N=115) or nortriptyline (N=126). The primary outcome measure was the score on the Montgomery-Åsberg Depression Rating Scale (MADRS), administered weekly. Results: CRP level at baseline differentially predicted treatment outcome with the two antidepressants (CRP-drug interaction: β=3.27, 95% CI=1.65, 4.89). For patients with low levels of CRP (<1 mg/L), improvement on the MADRS score was 3 points higher with escitalopram than with nortriptyline. For patients with higher CRP levels, improvement on the MADRS score was 3 points higher with nortriptyline than with escitalopram. CRP and its interaction with medication explained more than 10% of individual-level variance in treatment outcome. Conclusions: An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice.
Should smoking in outside public spaces be banned? Yes
Authors: G. Thomson, N. Wilson, R. Edwards, A. Woodward
Journal: BMJ (2008)

After success in stopping smoking in public buildings, campaigns are turning outdoors. <b>George Thomson and colleagues</b> argue that a ban will help to stop children becoming smokers but <b>Simon Chapman</b> (doi:10.1136/bmj.a2804) believes that it infringes personal freedom
A comparative study of atropine methonitrate, salbutamol, and their combination in airways obstruction.
Authors: R J Pierce, C J Allen, A H Campbell
Journal: Thorax (1979)

Dose-response relationships of the cholinergic antagonist, atropine methonitrate, and the beta-adrenergic agonist, salbutamol, were examined by cumulative dose techniques. A wet aerosol, 1.5 mg atropine methonitrate produced a maximum response. The response to 200 microgram of salbutamol from a pressurised aerosol was close to maximum. Secondly, the bronchodilator response of salbutamol microgram was compared with atropine methonitrate 2 mg and placebo in 18 asthmatic patients in a randomised crossover study. In 11 of them the bronchodilator response of the combination of salbutamol and atropine methonitrate was evaluated. Atropine methonitrate produced a similar peak bronchodilator effect to salbutamol, but its effect was more prolonged, the response being significantly greater at four and six hours than with salbutamol. The combination of drugs produced a significantly greater and more lasting bronchodilatation than either of the drugs alone. Despite mild side effects, atropine methonitrate, either alone or in combination with an adrenergic drug, appears to have a place in the treatment of sever reversible airway obstruction not adequately controlled by conventional treatment.
Survival impact of epidermal growth factor receptor overexpression in patients with non-small cell lung cancer: a meta-analysis
Authors: H Nakamura
Journal: Thorax (2005)

Reorganization of residual descending motor circuits underlies poststroke recovery. We previously clarified a causal relationship between the cortico-rubral tract and intensive limb use-induced functional recovery after internal capsule hemorrhage (ICH). However, other descending tracts, such as the cortico-reticular tract, might also be involved in rehabilitation-induced compensation. To investigate whether rehabilitation-induced recovery after ICH involves a shift in the compensatory circuit from the cortico-rubral tract to the cortico-reticular tract, we established loss-of-function of the cortico-rubral tract or/and cortico-reticular tract using two sets of viral vectors comprising the Tet-on system and designer receptors exclusively activated by the designer drug (DREADD) system. We used an ICH model that destroyed almost 60% of the corticofugal fibers. Anterograde tracing in rehabilitated rats revealed abundant sprouting of axons from the motor cortex in the red nucleus but not in the medullary reticular formation during the early phase of recovery. This primary contribution of the cortico-rubral tract was demonstrated by its selective blockade, while selective cortico-reticular tract silencing had little effect. Interestingly, cortico-rubral tract blockade from the start of rehabilitation induced an obvious increase of axon sprouting in the reticular formation with substantial functional recovery. Additional cortico-reticular tract silencing under the cortico-rubral tract blockade significantly worsened the recovered forelimb function. Furthermore, the alternative recruitment of the cortico-reticular tract was gradually induced by intensive limb use under cortico-rubral tract blockade, in which cortico-reticular tract silencing caused an apparent motor deficit. These findings indicate that individual cortico-brainstem pathways have dynamic compensatory potency to support rehabilitative functional recovery after ICH. <b>SIGNIFICANCE STATEMENT</b> This study aimed to clarify the interaction between the cortico-rubral and the cortico-reticular tract during intensive rehabilitation and functional recovery after capsular stroke. Pathway-selective disturbance by two sets of viral vectors revealed that the cortico-rubral tract was involved in rehabilitation-induced recovery of forelimb function from an early phase after internal capsule hemorrhage, but that the cortico-reticular tract was not. The sequential disturbance of both tracts revealed that the cortico-reticular tract was recruited and involved in rehabilitation-induced recovery when the cortico-rubral tract failed to function. Our data demonstrate a dynamic compensatory action of individual cortico-brainstem pathways for recovery through post-stroke rehabilitation.
A Virus in Rheumatism
Authors: G. H. Eagles
Journal: Annals of the Rheumatic Diseases (1939)

immune serum, the evidence from the standpoint of agglutination was, at least, highly suggestive.There remained two main avenues of inquiry to be explored.First, to apply similar technique to other members of the rheumatic group of diseases to discover, if possible, a common factor; and second, and most important, to ascertain if these particles could be shown to possess infectivity.It must be clearly understood that morpho- logical and serological data are not sufficient proof that these particles are true virus bodies, or that they are the causative agent of the disease from which they were isolated.Eagles, Evans, Fisher and Keith (1937) have repeated the work of Schlesinger and his co-workers, and at the same time extended their observations to include rheumatoid arthritis and acute chorea.By methods of high-speed and differential cen- trifugation they obtained particle suspensions from pericardial, pleural and joint fluids and fibrin in " bread and butter " pericarditis from cases of acute rheumatic fever, from joint fluids, joint washings, and synovial membrane in rheumatoid arthritis, and from cerebro-spinal fluid in a fatal case of chorea with carditis and nodules.These suspensions in stained smear preparations and under dark-ground illumination were indis- tinguishable from known virus elementary bodies.They also bore a close resemblance to suspensions prepared from exudates from non-rheumatic sources.Suspensions of particles may be prepared from any infective pathological exudate and cannot be distinguished on morphology alone from rheumatic sus- pensions.Since these particles are not confined to rheumatic infection, agglutination reactions were used to test their relation to rheu- matism.The technique used was identical with that employed by Schlesinger and his co-workers.Equal parts of suspension and test serum in suitable dilutions were mixed in hanging-drop preparations, incubated at room temperature and examined on successive days by low power of the microscope.Positive agglutination was shown by the presence of small, highly refractile clumps appearing after twenty-four to forty-eight hours.In negative tests the suspension settled out on the bottom of the drop in an even ground-glass-like deposit.Sera were selected to include patients suffering from rheumatism of various types- acute rheumatic fever, acute, subacute and chronic rheumatoid arthritis, chorea with and without carditis, and an occasional 19 copyright.
Aortic Input Impedance during Nitroprusside Infusion
Authors: Carl J. Pepine, W. W. Nichols, R. C. Curry, C. Richard Conti
Journal: Journal of Clinical Investigation (1979)

Beneficial effects of nitroprusside infusion in heart failure are purportedly a result of decreased afterload through "impedance" reduction. To study the effect of nitroprusside on vascular factors that determine the total load opposing left ventricular ejection, the total aortic input impedance spectrum was examined in 12 patients with heart failure (cardiac index <2.0 liters/min per m2 and left ventricular end diastolic pressure >20 mm Hg). This input impedance spectrum expresses both mean flow (resistance) and pulsatile flow (compliance and wave reflections) components of vascular load. Aortic root blood flow velocity and pressure were recorded continuously with a catheter-tip electromagnetic velocity probe in addition to left ventricular pressure. Small doses of nitroprusside (9-19 μg/min) altered the total aortic input impedance spectrum as significant (P < 0.05) reductions in both mean and pulsatile components were observed within 60-90 s. With these acute changes in vascular load, left ventricular end diastolic pressure declined (44%) and stroke volume increased (20%, both P < 0.05). Larger nitroprusside doses (20-38 μg/min) caused additional alteration in the aortic input impedance spectrum with further reduction in left ventricular end diastolic pressure and increase in stroke volume but no additional changes in the impedance spectrum or stroke volume occurred with 39-77 μg/min. Improved ventricular function persisted when aortic pressure was restored to control values with simultaneous phenylephrine infusion in three patients. These data indicate that nitroprusside acutely alters both the mean and pulsatile components of vascular load to effect improvement in ventricular function in patients with heart failure. The evidence presented suggests that it may be possible to reduce vascular load and improve ventricular function independent of aortic pressure reduction.
The diagnostic value of serum soluble CD 14 and IL-10 levels in newly diagnosed pulmonary tuberculosis patients and the relationship with disease extensity
Authors: Oguz Ozgedik, Nevin Taci Hoca, Ufuk Onde, Filiz Cimen, Sukran Atikcan, Mihriban Ogretensoy
Journal: European Respiratory Journal (2013)

Introduction: Soluble CD14 and IL-10 are markers that are involved in the pathogenesis of tuberculosis and still being investigated.  Aim: To evaluate the diagnostic value of serum soluble CD14 and IL-10 levels in newly diagnosed smear positive pulmonary tuberculosis patients and the relationship with disease extensity  Method: Thirty new cases of smear positive pulmonary tuberculosis (group I), thirty cases of smear positive pulmonary tuberculosis that were treated and cured with antituberculosis treatment (group II) and twenty seven healthy cases (group III) were included to the study.  Results: Serum sCD14 levels were found significantly higher in group I when compared with group II. However, no statistically difference was found between group I and III. The serum sCD14 levels of group III were found significantly higher than group II. No statistically significant difference was found in the serum IL-10 levels between the groups. Also we examined the relationship between serum sCD14, IL-10 levels and radiologic extent and the presence of cavity in new cases of smear positive tuberculosis patients. No statistically difference was found between the groups radiologically separated as mild, moderate, and severe disease, between cases of cavity and without cavity.  Conclusion: No association between serum level of IL-10 and pulmonary tuberculosis was found. These results highlight the need for further evaluation of the roll of sCD14 and IL-10 in the diagnosis of tuberculosis, predicting the severity of disease and especially follow-up of therapy success with larger groups of patients.
A call for an expanded synthesis of developmental and evolutionary paradigms
Authors: Andrew J. Lewis
Journal: Behavioral and Brain Sciences (2012)

Charney's target article continues a critique of genetic blueprint models of development that suggests reconsideration of concepts of adaptation, inheritance, and environment, which can be well illustrated in current research on infant attachment. The concepts of development and adaptation are so heavily based on the model of genetics and inheritance forged in the modern synthesis that they will require reconsideration to accommodate epigenetic inheritance.
Chromosome 19 Translocation, Overexpression of Notch3, and Human Lung Cancer
Authors: T. P. Dang, A. F. Gazdar, A. K. Virmani, T. Sepetavec, K. R. Hande, J. D. Minna, J. R. Roberts, D. P. Carbone
Journal: JNCI Journal of the National Cancer Institute (2000)

Somatically acquired chromosometranslocations are the major mechanismfor gene activation in hematologic ma-lignancies, but they have not been de-scribed previously in the more commonepithelial tumors, such as lung cancers.Furthermore, lung carcinomas often ex-hibit complex karyotypes, and this com-plexity has been assumed to imply a lackof specificity. Indeed, chromosomal de-letions associated with mutations in tu-mor suppressor genes, or gene amplifi-cations of dominant oncogenes, arewell-known genetic abnormalities inthese tumors
Abstract IA5-3: HIFs, hypoxia, and tumor progression
Authors: M. Celeste Simon
Journal: Clinical Cancer Research (2010)

Abstract Hypoxia-inducible factor (HIF)-1α and −2α display unique and sometimes opposing activities in regulating cellular energy homeostasis, cell fate decisions, and oncogenesis. To fully characterize hypoxic adaptations, distinct functions of HIF-1α versus HIF-2α must be elucidated. Macrophages accumulate both HIF-αS under hypoxia, but HIF-2α overexpression in tumor-associated macrophages (TAMs) is specifically correlated with high-grade human tumors and poor prognosis. HIF-1α regulates myeloid-mediated inflammatory and antibacterial activities, in part through control of glycolysis and ATP production. However, the precise role of HIF-2α during macrophage-mediated inflammatory responses remained unclear. We demonstrate here that mice lacking myeloid HIF-2α are resistant to lipopolysaccharide-induced endotoxemia and display a marked inability to mount inflammatory responses to cutaneous and peritoneal irritants. Furthermore, HIF-2α directly regulates pro-inflammatory cytokine/chemokine expression in macrophages activated in vitro. Using independent murine hepatocellular and colitis-associated colon carcinoma models, we show that HIF-2α -deficient macrophages exhibit migratory defects associated with reduced tumor cell proliferation and progression. Of note, HIF-2α modulates macrophage migration by regulating the expression of cytokine receptor M-CSFR and chemokine receptor CXCR4, without altering intracellular ATP levels. Collectively, our data identify HIF-2α as an important regulator of innate immunity, suggesting it may be a useful therapeutic target for treating inflammatory disorders and cancer. Citation Information: Clin Cancer Res 2010;16(14 Suppl):IA5-3.
Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. XII. Fine specificity of anti-idiotypic suppressor T cells (Ts2).
Authors: D H Sherr, S T Ju, M E Dorf
Journal: The Journal of Experimental Medicine (1981)

The fine specificity of anti-idiotypic, effector-phase suppressor T cells (Ts2) induced by the intravenous injection of syngeneic spleen cells covalently coupled with the 4-hydroxy-3-nitrophenyl acetyl (NP) hapten was studied in an in vitro plaque-forming cell system. By comparing the ability of these suppressor cells to bind monoclonal anti-NP antibodies that express different levels of serologically detected NPb idiotypic determinants, it was shown that anti-idiotypic suppressor T cells do not recognize the predominant NPb idiotypic determinants that are defined by serologic analysis. The implications for the possible expression and/or recognition of different sets of idiotypic determinants on T and B cells are discussed.