tbuckley/cabot-search huggingface dataset:
Sibutramine versus continuous positive airway pressure in obese obstructive sleep apnoea patients
Authors: A. Ferland, P. Poirier, F. Series
Journal: European Respiratory Journal (2009)

The aim of the present study was to compare the efficacy of 1 yr of sibutramine-induced weight loss <i>versus</i> continuous positive airway pressure (CPAP) treatment on sleep-disordered breathing, cardiac autonomic function and systemic blood pressure in obese patients with obstructive sleep apnoea. Subjects with a body mass index of ≥30 kg·m<sup>−2</sup> without previous treatment for obstructive sleep apnoea underwent either sibutramine (n = 22) or CPAP (n = 18) treatment for 1 yr. Sibutramine induced a 5.4±1.4 kg decrease in body weight compared to the CPAP group, in which no changes in anthropometric variables were observed. The CPAP treatment improved all sleep and respiratory variables, whereas sibutramine-induced weight loss improved only nocturnal arterial oxygen saturation profile. Only CPAP treatment improved night-time systolic and diastolic blood pressure and 24-h and daytime ambulatory diastolic blood pressure. Sibutramine-induced weight loss had no impact on indices of heart rate variability, whereas CPAP treatment increased daytime time domain indices. CPAP treatment for 1 yr had beneficial impacts on nocturnal breathing disturbances, and improved nocturnal oxygenation, night-time systolic and diastolic blood pressure, and daytime cardiac parasympathetic modulation. Sibutramine did not improve sleep-disordered breathing, systemic blood pressure or heart rate variability. There were no adverse effects, such as increment in blood pressure or arrhythmias, associated with this treatment regimen.
Abolition of methacholine induced bronchoconstriction by the hyperventilation of exercise or volition.
Authors: S Freedman, R Lane, M K Gillett, A Guz
Journal: Thorax (1988)

Total pulmonary resistance was measured from continuous records of flow and oesophageal pressure in five normal subjects on three separate days before and after inhalation of methacholine. The dose of methacholine produced, on average, a fivefold increase in airway resistance. Immediately after methacholine inhalation the subjects underwent a progressive exercise test on a cycle ergometer (day 1) or voluntary hyperventilation (day 2) or remained resting (day 3). On the first day during exercise pulmonary resistance fell rapidly to baseline levels within two to three minutes and remained there for the 10 minute duration of the exercise. On day 2 voluntary reproduction of the same level and pattern of ventilation as during exercise resulted in a similar fall of resistance. On the third day, when the subjects remained at rest, pulmonary resistance remained raised for 10 minutes. It is concluded that the bronchodilator effects of exercise can be explained by the increased ventilation rather than the exercise itself, but with much smaller tidal volumes than have previously been thought necessary to reduce drug induced bronchoconstriction.
Prognostic factors in patients with pleural mesothelioma: the European Organization for Research and Treatment of Cancer experience.
Authors: D Curran, T Sahmoud, P Therasse, J van Meerbeeck, P E Postmus, G Giaccone
Journal: Journal of Clinical Oncology (1998)

PURPOSE Identification of prognostic factors in patients with malignant pleural mesothelioma based on prospectively collected international data. PATIENTS AND METHODS From October 1984 to October 1993, 204 eligible adult patients with malignant pleural mesothelioma were entered into five consecutive prospective European Organization for Research and Treatment of Cancer (EORTC) phase II clinical trials designed to assess the efficacy of various anticancer drugs (mitoxantrone, epidoxorubicin, etoposide, and paclitaxel). The Cox model was used to assess 13 factors related to biology and disease history with respect to survival. RESULTS The median survival duration was 12.6 months from diagnosis and 8.4 months from trial entry. In the multivariate analysis, poor prognosis was associated with a poor performance status, a high WBC count, a probable/possible histologic diagnosis of mesothelioma, male gender, and having sarcomatous tissue as the histologic subtype. Taking these five factors into consideration, patients were classified into two groups: a good-prognosis group (1-year survival rate, 40%; 95% confidence interval [CI], 30% to 50%) and a poor-prognosis group (1-year survival, 12%; 95% CI, 4% to 20%). CONCLUSION These results may help to design new clinical trials in pleural mesothelioma by selecting more homogenous groups of patients.
Diagnostic delay in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis: results from the Danish nationwide DANBIO registry
Authors: Jan Sørensen, Merete Lund Hetland
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background/purpose</h3> Early diagnosis of inflammatory rheumatic diseases is important in order to improve long-term outcome. We studied whether delay in diagnosis (time between onset of symptoms and establishment of diagnosis) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PSA) and ankylosing spondylitis (AS) changed from year 2000 to 2011. <h3>Methods</h3> Month and year of initial symptoms and diagnosis, gender, hospital, year of birth and date of first data entry were obtained for 13 721 patients with RA, PSA or AS who had been registered in the DANBIO registry. Time between symptom onset and diagnosis was modelled using generalised linear regression to predict the average duration for each calendar year of initial symptoms with adjustments for gender, year of birth and date of DANBIO entry. <h3>Results</h3> Patients with valid data (RA: 10 416 (73%); PSA: 1970 (68%); AS: 1335 (65%)) did not differ significantly from the whole DANBIO population, except more missing data in early years. The regression model showed that the mean duration from initial symptoms to diagnosis for RA, PSA and AS declined steadily from 30, 53 and 66 months (year 2000), respectively, to 3–4 months (year 2011). Sensitivity analyses including patients who were included after 2005, patients who had received biological treatment or had symptom onset less than 2 and 5 years prior to first entry into DANBIO showed similar results. <h3>Conclusion</h3> Since the year 2000, a significant reduction in diagnostic delay was observed in this large cohort of patients with RA, PSA or AS, probably reflecting a stronger awareness of the importance of early diagnosis.
Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes.
Authors: M C Cuturi, M Murphy, M P Costa-Giomi, R Weinmann, B Perussia, G Trinchieri
Journal: The Journal of Experimental Medicine (1987)

We present evidence that human peripheral blood lymphocytes, free of contaminating monocytes, rapidly produce high levels of tumor necrosis factor (TNF) when stimulated with phorbol diester and calcium ionophore, and lower but significant levels of TNF when stimulated with mitogens. These two types of inducers act preferentially on T cells, both CD4+ and CD8+. NK cells produce TNF only when stimulated with phorbol diester and calcium ionophore, and they do so at a much lower level than T cells. The procedures used in the purification of lymphocytes and the differential ability to respond to various inducers allow us to exclude that monocytes or basophils contaminating the lymphocyte preparation participate in the production of TNF. In particular, LPS, a potent inducer of TNF production from monocytes, is unable to induce significant levels of TNF in the lymphocyte preparations. The TNF produced by lymphocytes has antigenic, physicochemical, and biochemical characteristics identical to those of the TNF produced by myeloid cell lines or monocytes upon stimulation with LPS. LT is also produced by lymphocyte preparations. Production of TNF and LT proteins in response to the different inducers is paralleled by accumulation of cytoplasmic TNF and LT mRNA. Both at mRNA and at protein levels, stimulation of T lymphocytes with phorbol diester and calcium ionophore preferentially induces TNF, whereas mitogen stimulation preferentially induces LT. Our data suggest that the TNF and LT genes, two closely linked genes encoding two partially homologous proteins with almost identical biological functions, are independently regulated in lymphocytes.
Rapamycin Rescues ABT-737 Efficacy in Small Cell Lung Cancer
Authors: Eric E. Gardner, Nick Connis, John T. Poirier, Leslie Cope, Irina Dobromilskaya, Gary L. Gallia, Charles M. Rudin, Christine L. Hann
Journal: Cancer Research (2014)

Overexpression of the antiapoptotic protein Bcl-2 is observed in the majority of small cell lung cancer (SCLC) cases and is associated with resistance to chemotherapy. While targeting Bcl-2 in hematologic malignancies continues to show signs of promise, translating the BH3 mimetic ABT-737 (or ABT-263; navitoclax) to the clinic for solid tumors has remained problematic, with limited single-agent activity in early-phase clinical trials. Here, we used patient-derived xenograft (PDX) models of SCLC to study ABT-737 resistance and demonstrated that responses to ABT-737 are short lived and coincide with decreases in HIF-1α-regulated transcripts. Combining the mTOR inhibitor rapamycin with ABT-737 rescued this resistance mechanism, was highly synergistic in vitro, and provided durable tumor regressions in vivo without notable hematologic suppression. In comparison, tumor regressions did not occur when ABT-737 was combined with etoposide, a gold-standard cytotoxic for SCLC therapy. Rapamycin exposure was consistently associated with an increase in the proapoptotic protein BAX, whereas ABT-737 caused dose-dependent decreases in BAX. As ABT-737 triggers programmed cell death in a BAX/BAK-dependent manner, we provide preclinical evidence that the efficacy of ABT-737 as a single agent is self-limiting in SCLC, but the addition of rapamycin can maintain or increase levels of BAX protein and markedly enhance the anticancer efficacy of ABT-737. These data have direct translational implications for SCLC clinical trials.
Effect of loratadine, an H1 antihistamine, on induced cough in non-asthmatic patients with chronic cough.
Authors: S. Tanaka, K. Hirata, N. Kurihara, J. Yoshikawa, T. Takeda
Journal: Thorax (1996)

H1 antihistamines have been shown to have an antitussive effect in patients with asthma, postnasal drip, and allergic rhinitis. No study has been performed to determine whether orally administered H1 antihistamines can reduce the number of coughs induced by stimulation of cough receptors in non-asthmatic patients with chronic dry cough.The effect of loratadine (10 mg) on the number of coughs induced by ultrasonically nebulised distilled water (UNDW) was examined in 10 patients with nasal disease and in seven patients with unexplained chronic cough using a randomised, double blind crossover method. Eleven normal volunteers were also studied. Each subject inhaled UNDW for one minute, and the numbers of coughs during the one minute inhalation and the 30 seconds following it were counted.There was no difference in the results of pulmonary function tests performed before and one minute after UNDW inhalation for either patients or normal subjects. There was also no significant difference between the results of pulmonary function tests before or after oral administration of loratadine. Loratadine significantly reduced the number of coughs in patients with nasal disease and in those with unexplained chronic cough, but not in normal subjects.The H1 antihistamine loratadine reduces cough induced by UNDW. The release of histamine may contribute to the chronic cough in patients with unexplained chronic cough or nasal disease.
Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide-induced vascular inflammation
Authors: Rajesh Kumar Gandhirajan, Shu Meng, Harish C. Chandramoorthy, Karthik Mallilankaraman, Salvatore Mancarella, Hui Gao, Roshanak Razmpour, Xiao-Feng Yang, Steven R. Houser, Ju Chen, Walter J. Koch, Hong Wang, Jonathan Soboloff, Donald L. Gill, Muniswamy Madesh
Journal: Journal of Clinical Investigation (2013)

During sepsis, acute lung injury (ALI) results from activation of innate immune cells and endothelial cells by endotoxins, leading to systemic inflammation through proinflammatory cytokine overproduction, oxidative stress, and intracellular Ca2+ overload. Despite considerable investigation, the underlying molecular mechanism(s) leading to LPS-induced ALI remain elusive. To determine whether stromal interaction molecule 1–dependent (STIM1-dependent) signaling drives endothelial dysfunction in response to LPS, we investigated oxidative and STIM1 signaling of EC-specific Stim1-knockout mice. Here we report that LPS-mediated Ca2+ oscillations are ablated in ECs deficient in Nox2, Stim1, and type II inositol triphosphate receptor (Itpr2). LPS-induced nuclear factor of activated T cells (NFAT) nuclear accumulation was abrogated by either antioxidant supplementation or Ca2+ chelation. Moreover, ECs lacking either Nox2 or Stim1 failed to trigger store-operated Ca2+ entry (SOCe) and NFAT nuclear accumulation. LPS-induced vascular permeability changes were reduced in EC-specific Stim1–/– mice, despite elevation of systemic cytokine levels. Additionally, inhibition of STIM1 signaling prevented receptor-interacting protein 3–dependent (RIP3-dependent) EC death. Remarkably, BTP2, a small-molecule calcium release–activated calcium (CRAC) channel blocker administered after insult, halted LPS-induced vascular leakage and pulmonary edema. These results indicate that ROS-driven Ca2+ signaling promotes vascular barrier dysfunction and that the SOCe machinery may provide crucial therapeutic targets to limit sepsis-induced ALI.
6-minute walk testing in COPD: is it reproducible?
Authors: G. Criner
Journal: European Respiratory Journal (2011)

The 6-min walk test (6MWT) has historically been used to characterise the functional status of chronic obstructive pulmonary disease (COPD) patients. However, over the past few years, the 6MWT has assumed a more central role in the assessment and management of COPD. In COPD, the 6MWT is now routinely used as an outcome measure in clinical trials [1, 2], a prognostic indicator either by itself [3] or as part of a multidimensional index [4], and as a functional threshold that patients must achieve before being considered acceptable candidates for lung volume reduction surgery (LVRS) [2] or lung transplantation [5]. Much of the attraction of the 6MWT as an assessment tool in COPD is due to its simplicity of performance, inexpensiveness, responsiveness to standardisation and embodiment of an important functional task ( i.e. ambulation). New insights that the manifestations of COPD go well beyond the lung, and include its cardiac and peripheral muscle wasting effects, are additional factors that make a test of functional performance like the 6MWT attractive as an assessment tool [6]. However, to be considered a reliable tool in the assessment of COPD patients, the performance of the 6MWT must be proven to be reproducible in clinical trials as well as in commonly encountered clinical settings.

Many variables may affect the performance of a 6MWT. These variables include course length, course layout (linear, oval or continuous circle), whether a …
Definition and Measurement of Follicle Stimulating Hormone
Authors: Matthew P. Rose, Rose E. Gaines Das, Adam H. Balen
Journal: Endocrine Reviews (2000)

Abstract FSH has a key role in the development and function of the reproductive system and is widely used both diagnostically and therapeutically in developmental and reproductive medicine. The accurate measurement of FSH levels, in patients for diagnosis and monitoring and in therapeutic preparations for clinical use, is essential for safe and successful treatment. Historically, FSH was defined on the basis of classical in vivo endocrine activity, and early therapeutic preparations were calibrated using in vivo bioassays. There was early recognition that reference preparations were required for calibration if the results from different laboratories were to be comparable. In response to the perceived need, the World Health Organization established the first standard for such preparations in 1959. Subsequent developments in biotechnology have led to recognition that there is no single molecule that can be uniquely defined as FSH, and that FSH can induce a range of biological activities. Several highly purified standards for FSH are now available, but discontinuity and heterogeneity of estimates of FSH activity in terms of these standards made using in vitro assays and binding assays have been noted. It is thus essential that any measurement of FSH include specification both of the standard with which the measured FSH is compared and the assay method used for that comparison.
Bacterial contamination of enteral diets.
Authors: I H de Leeuw, M F Vandewoude
Journal: Gut (1986)

Enteral feeding solutions can be contaminated by bacterial micro-organisms already present in the ingredients, or introduced during preparation or transport, or in the hospital ward. During jejunostomy feeding without pump or filter, ascending bacterial invasion of the feeding bag is possible. In patients with lowered immune response contaminated feedings can cause serious septic clinical problems. The progressive loss of the nutritional value of the enteral feeding solution by bacterial contamination has to be considered for all patients.
ROLE OF CYTOKINES IN RHEUMATOID ARTHRITIS
Authors: Marc Feldmann, Fionula M. Brennan, Ravinder N. Maini
Journal: Annual Review of Immunology (1996)

▪ Abstract Analysis of cytokine mRNA and protein in rheumatoid arthritis tissue revealed that many proinflammatory cytokines such as TNFα, IL-1, IL-6, GM-CSF, and chemokines such as IL-8 are abundant in all patients regardless of therapy. This is compensated to some degree by the increased production of anti-inflammatory cytokines such as IL-10 and TGFβ and cytokine inhibitors such as IL-1ra and soluble TNF-R. However, this upregulation in homeostatic regulatory mechanisms is not sufficient as these are unable to neutralize all the TNFα and IL-1 produced. In rheumatoid joint cell cultures that spontaneously produce IL-1, TNFα was the major dominant regulator of IL-1. Subsequently, other proinflammatory cytokines were also inhibited if TNFα was neutralized, leading to the new concept that the proinflammatory cytokines were linked in a network with TNFα at its apex. This led to the hypothesis that TNFα was of major importance in rheumatoid arthritis and was a therapeutic target. This hypothesis has been successfully tested in animal models, of, for example, collagen-induced arthritis, and these studies have provided the rationale for clinical trials of anti-TNFα therapy in patients with long-standing rheumatoid arthritis. Several clinical trials using a chimeric anti-TNFα antibody have shown marked clinical benefit, verifying the hypothesis that TNFα is of major importance in rheumatoid arthritis. Retreatment studies have also shown benefit in repeated relapses, indicating that the disease remains TNFα dependent. Overall these studies demonstrate that analysis of cytokine expression and regulation may yield effective therapeutic targets in inflammatory disease.
Pentraxin-chromatin interactions: serum amyloid P component specifically displaces H1-type histones and solubilizes native long chromatin.
Authors: P J Butler, G A Tennent, M B Pepys
Journal: The Journal of Experimental Medicine (1990)

Pure serum amyloid P component (SAP) and native long chromatin, mixed together at wt/wt ratios between 1:1 and 1:2 in the presence of physiological concentrations of NaCl and calcium, both remained in solution, whereas each alone precipitates rapidly under these conditions. This solubilization accompanies the binding of SAP to chromatin and the displacement of H1-type histones, which are essential for condensation and higher order folding of chromatin. Such binding of SAP to chromatin is remarkable since displacement of H1 and H5 by salt alone requires approximately 0.5 M NaCl. SAP also bound to nucleosome core particles forming soluble complexes with an apparent stoichiometry of 1:2, a result that is compatible with attachment of SAP at the nucleosome dyad, the site of H1 in intact chromatin. SAP thus undergoes a specific, avid interaction with chromatin that promotes its solubilization and may thereby contribute to the physiological handling of chromatin released from cells in vivo. In contrast, C-reactive protein (CRP) did not bind significantly to either chromatin or to core particles at physiological ionic strength. Incubation of chromatin with either normal serum, or acute phase human serum containing raised levels of CRP, did not induce complement activation regardless of the presence of added SAP or CRP, nor was any cleavage of DNA observed.
Inflammation Markers, Adhesion Molecules, and All-Cause and Cardiovascular Mortality in Patients with ESRD
Authors: Giovanni Tripepi, Francesca Mallamaci, Carmine Zoccali
Journal: Journal of the American Society of Nephrology (2005)

Inflammation is a major risk factor for mortality and cardiovascular (CV) complications in patients with ESRD. The predictive value of C-reactive protein (CRP) of the main proinflammatory cytokines (IL-1β, IL-6, IL-18, and TNF-α) and of two adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) in 217 dialysis patients was compared. Serum IL-6 and CRP added significant prediction power to the multivariate Cox model of all-cause death, and the gain in the prediction power attributable to IL-6 was approximately two times higher than that of CRP. Patients in the third tertiles of serum IL-6 and CRP had a relative risk of all-cause mortality 2.5 and 1.8 times higher than those in the first corresponding tertiles, and there was no statistical difference between these two relative risks. The gain in prediction power associated with TNF-α, IL-β, IL-18, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 was of small degree (P = NS). Similarly, serum IL-6 added the highest prediction power to the CV death model, and the IL-6 attributable gain was approximately two times higher than that of serum CRP. However, the risk estimate for CV mortality of patients with high serum IL-6 did not differ significantly from that of patients with high serum CRP. IL-6 adds significantly greater predictive power for all-cause and CV death to statistical models based on traditional and nontraditional risk factors in ESRD patients. However, the risk estimate by CRP being reasonably close to that of IL-6, CRP may be a cheap alternative to IL-6 in clinical practice.
Linear IgA dermatosis with severe arthralgia
Authors: GILLIAN LEIGH, R.A. MARSDEN, FENELLA WOJNAROWSKA
Journal: British Journal of Dermatology (1988)

Journal Article Linear IgA dermatosis with severe arthralgia Get access GILLIAN LEIGH, GILLIAN LEIGH Departments of Dermatology, St George's Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.A. MARSDEN, R.A. MARSDEN Departments of Dermatology, St George's Hospital, London, U.K. Dr R.A. Marsden, Department of Dermatology, St George's Hospital, London, SW170QT, U.K. Search for other works by this author on: Oxford Academic Google Scholar FENELLA WOJNAROWSKA FENELLA WOJNAROWSKA The Slade Hospital, Oxford, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 119, Issue 6, 1 December 1988, Pages 789–792, https://doi.org/10.1111/j.1365-2133.1988.tb03505.x Published: 01 December 1988