tbuckley/cabot-search huggingface dataset:
Follow up studies in rheumatoid arthritis
Authors: R Landewe
Journal: Annals of the Rheumatic Diseases (2002)

Do we really need follow up studies of randomised clinical trials in RA? In rheumatology we have been told for years that the results of randomised controlled trials may not be extrapolated to the long term, and that a gain in the beginning may not necessarily mean a gain in what we solemnly call the “final outcome”. In almost every review on disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA), long term efficacy and long term toxicity are always considered. The importance of long term data is repeatedly stated, without, however, explaining what information is really necessary. And regulatory authorities nowadays require long term studies before approving drugs which claim, for example, to preserve function. Probably as a consequence of this, we are now facing an increasing number of published follow up reports of clinical trials—for example, references 1–6a.1–6a The conclusion is always that some drug is still as effective and as toxic as its comparator, x years after the start of the trial, or that drug A “maintains its efficacy or its superiority over drug B” over time. A large number of arguments are mentioned by different authors to justify follow up studies. These arguments—more or less valid—include doubts about long term clinical efficacy, effects on radiological progression and function, long term toxicity, “drug survival time”, cost effectiveness, and quality of life. Intuitively, follow ups of randomised controlled trials (RCTs) enjoy a greater respect than observational studies, because patients were allocated to groups by chance, and most authors assume they can make an appropriate between-group comparison at the end. The questions to be asked in this editorial are:
A randomised crossover trial of chest physiotherapy in non-cystic fibrosis bronchiectasis
Authors: M P Murray, J L Pentland, A T Hill
Journal: European Respiratory Journal (2009)

Regular chest physiotherapy is advocated in non-cystic fibrosis bronchiectasis despite little evidence supporting its routine use. This study aimed to establish the efficacy of regular chest physiotherapy in non-cystic fibrosis bronchiectasis compared with no regular chest physiotherapy. 20 patients not practising regular chest physiotherapy were enrolled in a randomised crossover trial of 3 months of twice daily chest physiotherapy using an oscillatory positive expiratory pressure device compared with 3 months of no chest physiotherapy. The primary end-point was the Leicester Cough Questionnaire (LCQ). Additional outcomes included 24-h sputum volume, forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF(25-75%)), maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), exercise capacity, sputum microbiology and St George's Respiratory Questionnaire (SGRQ). The treatment effect was estimated using the differences of the pairs of observations from each patient. There was a significant improvement in all domains and total LCQ score with regular chest physiotherapy (median (interquartile range) total score improvement 1.3 (-0.17-3.25) units; p = 0.002). 24-h sputum volume increased significantly with regular chest physiotherapy (2 (0-6) mL; p = 0.02), as did exercise capacity (40 (15-80) m; p = 0.001) and SGRQ total score (7.77 (-0.99-14.5) unit improvement; p = 0.004). No significant differences were seen in sputum bacteriology, FEV(1), FVC, FEF(25-75%), MIP or MEP. Regular chest physiotherapy in non-cystic fibrosis bronchiectasis has small, but significant benefits.
Predictors of mortality in acute lung injury during the era of lung protective ventilation
Authors: E Seeley, D F McAuley, M Eisner, M Miletin, M A Matthay, R H Kallet
Journal: Thorax (2008)

<h3>Background:</h3> Lung protective ventilation has been widely adopted for the management of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Consequently, ventilator associated lung injury and mortality have decreased. It is not known if this ventilation strategy changes the prognostic value of previously identified demographic and pulmonary predictors of mortality, such as respiratory compliance and the arterial oxygen tension to inspired oxygen fraction ratio (Pao<sub>2</sub>/Fio<sub>2</sub>). <h3>Methods:</h3> Demographic, clinical, laboratory and pulmonary variables were recorded in 149 patients with ALI/ARDS. Significant predictors of mortality were identified in bivariate analysis and these were entered into multivariate analysis to identify independent predictors of mortality. <h3>Results:</h3> Hospital mortality was 41%. In the bivariate analysis, 17 variables were significantly correlated with mortality, including age, APACHE II score and the presence of cirrhosis. Pulmonary parameters associated with death included Pao<sub>2</sub>/Fio<sub>2</sub> and oxygenation index ((mean airway pressure×Fio<sub>2</sub>×100)÷Pao<sub>2</sub>). In unadjusted analysis, the odds ratio (OR) of death for Pao<sub>2</sub>/Fio<sub>2</sub> was 1.57 (CI 1.12 to 3.04) per standard deviation decrease. However, in adjusted analysis, Pao<sub>2</sub>/Fio<sub>2</sub> was not a statistically significant predictor of death, with an OR of 1.29 (CI 0.82 to 2.02). In contrast, oxygenation index (OI) was a statistically significant predictor of death in both unadjusted analysis (OR 1.89 (CI 1.28 to 2.78)) and in adjusted analysis (OR 1.84 (CI 1.13 to 2.99)). <h3>Conclusions:</h3> In this cohort of patients with ALI/ARDS, OI was an independent predictor of mortality, whereas Pao<sub>2</sub>/Fio<sub>2</sub> was not. OI may be a superior predictor because it integrates both airway pressure and oxygenation into a single variable.
Association Between Vaccines and Neuroinflammation
Authors: Giovanni Ristori, Rosella Mechelli, Marco Salvetti
Journal: JAMA Neurology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Suppression of rejection of Nippostrongylus brasiliensis in iron and protein deficient rats: effect of syngeneic lymphocyte transfer.
Authors: A G Cummins, V M Duncombe, T D Bolin, A E Davis, J D Kelly
Journal: Gut (1978)

Rejection of Nippostrongylus brasiliensis is impaired in iron and protein deficient rats and this suggests that iron and protein deficiency directly or indirectly suppresses the immune response. The site of the immunological defect in deficient rats was investigated using the technique of cellular transfer of resistance. The functional activity of immune mesenteric lymph node cells obtained from iron and protein deficient donors was not depressed as measured by their capacity to cause parasite rejection in nutritionally sufficient recipients. In contrast, immune lymph node cells obtained from either sufficient or deficient donors did not result in parasite rejection in iron and protein deficient recipients. These results indicate that there is no permanent defect of lymphocyte function in iron and protein deficient rats and suggest that either some other component of the rejection mechanism is defective, or that lymphocyte function is blocked in an iron and protein deficient environment.
Bronchial responsiveness to inhaled methacholine in epidemiological studies: comparison of different indices
Authors: C Bruschi, I Cerveri, MC Zoia, L Maccarini, M Grassi, C Rampulla
Journal: European Respiratory Journal (1989)

We evaluated the sensitivity and specificity of different indices drawn from the forced expiratory curve in order to detect the best one for evaluating bronchial reactivity in the general population, and particularly, for distinguishing between normal and asthmatic subjects. 654 subjects, between 15 and 64 years of age, who were representative for age and sex of the general population of a small Lombardy town (Italy), were studied. Of the total sample, 448 subjects were clinically normal and asymptomatic, 87 were symptomatic or with acute upper respiratory disease within 30 days before the challenge with methacholine, 43 with allergic rhinitis, 26 asthmatics and 50 chronic bronchitics. All the subjects who had a baseline FEV1 greater than 85% predicted underwent methacholine challenge. Provocative LnDoses of a 6, 10, 15% fall in FEV1 (LnPD6, LnPD10, LnPD15) and provocative LnDose causing FEV1 to fall more than 2 SD below the mean of 5 FEV1 measurements following buffer inhalation (LnTD) were evaluated. Furthermore we calculated the "Dose-Response slope" (SL) proposed by O'Connor. The cut-off value of each index to define a responder was calculated by discriminant analysis of the response to the challenge in normal and in the asthmatic group. Sensitivity, specificity and predictive value of LnPD6, LnTD and SL were 79, 74, 14%; 71, 74, 13% and 46, 97, 48% respectively. LnPD10 had the best sensitivity (83%) with a high specificity (83%), but, as compared to LnPD15, whose sensitivity was 79% and specificity 89%, a lower predictive value (21% vs 27%).(ABSTRACT TRUNCATED AT 250 WORDS)
Targeting the BRAF V600E Mutation in Multiple Myeloma
Authors: Mindaugas Andrulis, Nicola Lehners, David Capper, Roland Penzel, Christoph Heining, Jennifer Huellein, Thorsten Zenz, Andreas von Deimling, Peter Schirmacher, Anthony D. Ho, Hartmut Goldschmidt, Kai Neben, Marc S. Raab
Journal: Cancer Discovery (2013)

Abstract In multiple myeloma, there has been little progress in the specific therapeutic targeting of oncogenic mutations. Whole-genome sequencing data have recently revealed that a subset of patients carry an activating mutation (V600E) in the BRAF kinase. To uncover the clinical relevance of this mutation in multiple myeloma, we correlated the mutation status in primary tumor samples from 379 patients with myeloma with disease outcome. We found a significantly higher incidence of extramedullary disease and a shorter overall survival in mutation carriers when compared with controls. Most importantly, we report on a patient with confirmed BRAF V600E mutation and relapsed myeloma with extensive extramedullary disease, refractory to all approved therapeutic options, who has rapidly and durably responded to low doses of the mutation-specific BRAF inhibitor vermurafenib. Collectively, we provide evidence for the development of the BRAF V600E mutation in the context of clonal evolution and describe the prognostic and therapeutic relevance of this targetable mutation. Significance: This is the first evidence of the clinical and therapeutic relevance of BRAF V600E mutations in multiple myeloma, proving the principle of specific inhibition of driver mutations in this disease. Cancer Discov; 3(8); 862–9. ©2013 AACR. See related commentary by O'Donnell and Raje, p. 840 This article is highlighted in the In This Issue feature, p. 826
Prospective Risk of Pancreatic Cancer in Familial Pancreatic Cancer Kindreds
Authors: Alison P. Klein, Kieran A. Brune, Gloria M. Petersen, Michael Goggins, Anne C. Tersmette, G. Johan A. Offerhaus, Constance Griffin, John L. Cameron, Charles J. Yeo, Scott Kern, Ralph H. Hruban
Journal: Cancer Research (2004)

Abstract Individuals with a family history of pancreatic cancer have an increased risk of developing pancreatic cancer. Quantification of this risk provides a rational basis for cancer risk counseling and for screening for early pancreatic cancer. In a prospective registry-based study, we estimated the risk of pancreatic cancer in individuals with a family history of pancreatic cancer. Standardized incidence ratios were calculated by comparing the number of incident pancreatic cancers observed with those expected using Surveillance, Epidemiology and End Results (SEER) rates. Familial pancreatic cancer (FPC) kindreds were defined as kindreds having at least one pair of first-degree relatives with pancreatic cancer, and sporadic pancreatic cancer (SPC) kindreds as families without such an affected pair. Nineteen incident pancreatic cancers developed among 5,179 individuals from 838 kindreds (at baseline, 370 FPC kindreds and 468 SPC kindreds). Of these 5,179 individuals, 3,957 had at least one first-degree relative with pancreatic cancer and contributed 10,538 person-years of follow-up. In this group, the observed-to-expected rate of pancreatic cancer was significantly elevated in members of FPC kindreds [9.0; 95% confidence interval (CI), 4.5–16.1], but not in the SPC kindreds (1.8; 95% CI., 0.22–6.4). This risk in FPC kindreds was elevated in individuals with three (32.0; 95% CI, 10.2–74.7), two (6.4; CI, 1.8–16.4), or one (4.6; CI, 0.5–16.4) first-degree relative(s) with pancreatic cancer. Risk was not increased among 369 spouses and other genetically unrelated relatives. Risk was higher in smokers than in nonsmokers. Individuals with a strong family history of pancreatic cancer have a significantly increased risk of developing pancreatic cancer.
The Inhibitory Effect of Heme on Heme Formation In Vivo: Possible Mechanism for the Regulation of Hemoglobin Synthesis*
Authors: Robert C. Gallo
Journal: Journal of Clinical Investigation (1967)

1) The effect of hemin on heme synthesis was studied in vivo. Heme synthesis was measured by determining red cell (59)Fe uptake and glycine-2-(14)C incorporation into red cell hemin in normal CF(1) female mice.2) Both bovine and human hemin significantly decreased red cell (59)Fe uptake 48, 72, and 96 hours after hemin injection.3) Glycine-2-(14)C incorporation into red cell hemin was decreased to 50% of control values after the administration of hemin (90 mumoles per kg).4) There was no significant difference between the plasma iron of mice injected with hemin and the values in control groups.5) Protoporphyrin decreased the inhibitory effect of hemin on red cell (59)Fe uptake by 64%.6) There was no measurable effect of delta-aminolevulinic acid on hemin inhibition of red cell (59)Fe uptake.7) Data are presented to show that the effect of hemin is not by a dilution mechanism nor by a decrease in red cell maturation and subsequent release of reticulocytes into the peripheral blood. The findings are discussed in regard to the possible site of a negative feedback control of heme synthesis by heme.
HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial
Authors: Paul M Ridker, Jacques Genest, S Matthijs Boekholdt, Peter Libby, Antonio M Gotto, Børge G Nordestgaard, Samia Mora, Jean G MacFadyen, Robert J Glynn, John JP Kastelein
Journal: The Lancet (2010)
Discoidin Domain Receptor 1 on Bone Marrow–Derived Cells Promotes Macrophage Accumulation During Atherogenesis
Authors: Christopher Franco, Karen Britto, Eric Wong, Guangpei Hou, Su-Ning Zhu, Mian Chen, Myron I. Cybulsky, Michelle P. Bendeck
Journal: Circulation Research (2009)

Rationale : We described a critical role for the discoidin domain receptor (DDR)1 collagen receptor tyrosine kinase during atherosclerotic plaque development. Systemic deletion of Ddr1 in Ldlr −/− mice accelerated matrix accumulation and reduced plaque size and macrophage content. However, whether these effects reflected an independent role for macrophage DDR1 during atherogenesis remained unresolved. Methods : In the present study, we performed sex-mismatched bone marrow transplantation using Ddr1 +/+ ; Ldlr −/− and Ddr1 −/− ; Ldlr −/− mice to investigate the role of macrophage DDR1 during atherogenesis. Chimeric mice with deficiency of DDR1 in bone marrow–derived cells ( Ddr1 −/−→+/+ ) or control chimeric mice that received Ddr1 +/+ ; Ldlr −/− marrow ( Ddr1 +/+→+/+ ) were fed an atherogenic diet for 12 weeks. Results : We observed a 66% reduction in atherosclerosis in the descending aorta and a 44% reduction in plaque area in the aortic sinus in Ddr1 −/−→+/+ mice compared to Ddr1 +/+→+/+ mice. Furthermore, we observed a specific reduction in the number of donor-derived macrophages in Ddr1 −/−→+/+ plaques, suggesting that bone marrow deficiency of DDR1 attenuated atherogenesis by limiting macrophage accumulation in the plaque. We have also demonstrated that the effects of DDR1 on macrophage infiltration and accumulation can occur at the earliest stage of atherogenesis, the formation of the fatty streak. Deficiency of DDR1 limited the appearance of 5-bromodeoxyuridine–labeled monocytes/macrophages in the fatty streak and resulted in reduced lesion size in Ldlr −/− mice fed a high fat diet for 2 weeks. In vitro studies to investigate the mechanisms involved revealed that macrophages from Ddr1 −/− mice had decreased adhesion to type IV collagen and decreased chemotactic invasion of type IV collagen in response to monocyte chemoattractant protein-1. Conclusions : Taken together, our data support an independent and critical role for DDR1 in macrophage accumulation at early and late stages of atherogenesis.
The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): a randomised, single-blind trial
Authors: Paul S Myles, Kate Leslie, Matthew T V Chan, Andrew Forbes, Philip J Peyton, Michael J Paech, W Scott Beattie, Daniel I Sessler, P J Devereaux, Brendan Silbert, Thomas Schricker, Sophie Wallace
Journal: The Lancet (2014)
Two-Year Prospective Follow-Up of Children With a Prepubertal and Early Adolescent Bipolar Disorder Phenotype
Authors: Barbara Geller, James L Craney, Kristine Bolhofner, Michael J Nickelsburg, Marlene Williams, Betsy Zimerman
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Longitudinal outcomes of bipolar disorder with onset in the late teenage years or in adulthood have been reported, but little is known about the natural history of childhood-onset mania. This study sought to provide rates and predictors of recovery and relapse in children with a prepubertal and early adolescent bipolar disorder phenotype. METHOD: Eighty-nine consecutively ascertained outpatient subjects (mean age=10.9 years [SD=2.7]) received comprehensive research assessments, including separate interviews of mothers about their children and of children about themselves, at baseline and at 6, 12, 18, and 24 months after baseline. The study phenotype required DSM-IV mania with elation and/or grandiosity as one criterion to distinguish the study phenotype from a diagnosis of mania based on criteria overlapping with those for attention deficit hyperactivity disorder and to ensure that subjects had at least one of the two cardinal features of mania (i.e., elation and/or grandiosity). Subjects were treated by their own community practitioners. RESULTS: The proportions of subjects who recovered from mania and who relapsed after recovery were 65.2% and 55.2%, respectively. The mean time to recovery was 36.0 weeks (SD=25.0). Relapse occurred after a mean of 28.6 weeks (SD=13.2). Living with an intact biological family significantly predicted rate of recovery, and a low level of maternal warmth significantly predicted rate of relapse. CONCLUSIONS: The relatively poor outcomes of these subjects may be related to their phenotypic resemblance to severely ill adults with bipolar disorder who have mixed mania, continuous rapid cycling, psychosis, and treatment-resistant psychopathology. A lower level of effectiveness of mood stabilizers in children cannot be ruled out. Although the significance of maternal warmth as a predictor is consistent with reports in adult mania, the significance of intact family as a predictor may be unique to childhood mania.
Involvement of MMP-12 and phosphodiesterase type 4 in cigarette smoke-induced inflammation in mice
Authors: O. Leclerc, V. Lagente, J-M. Planquois, C. Berthelier, M. Artola, T. Eichholtz, C. P. Bertrand, F. Schmidlin
Journal: European Respiratory Journal (2006)

The aim of the present study was to characterise a mouse model of airways inflammation induced by cigarette smoke and to compare it with a lipopolysaccharide (LPS) model with regards to the efficacy of a PDE4 inhibitor (cilomilast), a corticosteroid (dexamethasone) and macrophage metalloelastase (MMP)-12 gene deletion. Cigarette smoke exposure for 3 days induced a time-dependent airway neutrophilia associated with an increased level of keratinocyte-derived chemokine (KC), macrophage inflammatory protein (MIP)-2, MIP-1α and MMP-9 in the bronchoalveolar lavage (BAL). LPS exposure also induced an increase in the number of neutrophils in BAL. Studies in MMP-12-/- mice showed that in contrast to the smoking model, MMP-12 did not have a critical role in LPS-induced inflammation. Both cilomilast and dexamethasone blocked LPS-induced neutrophilia in a dose-dependent manner. Cilomilast inhibited cigarette smoke-induced neutrophilia and MIP-1α, but only 10 mg·kg −1 of dexamethasone was effective. Both anti-inflammatory treatments had no effect on the levels of KC and MIP-2 in the BAL. Although the inflammatory response was very similar in the smoking model and LPS, the pharmacological modulation and the MMP-12 gene deletion highlighted the differences in the mechanisms involved. Furthermore, the cigarette smoke model seemed to better represent the situation described in chronic obstructive pulmonary disease patients. In conclusion, these differences underline the importance of using an acute smoke-exposure model to investigate potential new treatments for chronic obstructive pulmonary disease.
Diagnostic value of dominant T-cell clones in peripheral blood in 363 patients presenting consecutively with a clinical suspicion of cutaneous lymphoma
Authors: Marie-Hélène Delfau-Larue, Liliane Laroche, Janine Wechsler, Eric Lepage, Chantal Lahet, Marianne Asso-Bonnet, Martine Bagot, Jean-Pierre Farcet
Journal: Blood (2000)