tbuckley/cabot-search huggingface dataset:
Exacerbator subtypes in the tiotropium safety and performance in respimat (TIOSPIR™) trial
Authors: Peter Calverley, Daniel Dusser, Robert Wise, Gordon Pledger, Ronald Dahl, Achim Mueller, Jessica Montero Caballero, Antonio Anzueto
Journal: European Respiratory Journal (2014)

Background: The long-acting antimuscarinic antagonist (LAMA) tiotropium is used to prevent exacerbations of chronic obstructive pulmonary disease (COPD) but information is limited on how often these events occur during LAMA therapy and which factors predict exacerbations.

Methods: A post-hoc exploratory pooled analysis of COPD patients with and without COPD exacerbations in TIOSPIR was performed. Baseline characteristics discriminating between patients without exacerbation (yearly exacerbation rate [YER]=0), and infrequent (YER≤1) and frequent (YER>1) exacerbators during the trial were identified using descriptive statistics.

Results: Of 17,116 patients, 8774 reported no exacerbation,4896 one and 3446 more than one exacerbation. Some baseline characteristics were similar between groups (age, body mass index) but patients reporting exacerbations were more likely to be female, have a history of frequent exacerbations, have lower mean forced expiratory volume in 1 s (FEV1) (GOLD III/IV) and to use more long-acting β2-agonists (LABA) and inhaled corticosteroids (ICS) at baseline (table).

View this table:



Conclusions: The large TIOSPIR dataset supports the relationship between established predictive variables, like lung function and exacerbation history, and exacerbation risk, also during LAMA therapy. Age, BMI and male gender had no prognostic adverse influence on exacerbations.

Funded by Boehringer Ingelheim.
Myocardial perfusion after aortocoronary bypass surgery: measurements at rest and after administration of isoproterenol.
Authors: D H Schmidt, F M Blau, L J Hendrix, M L Kamath, G Ray
Journal: Circulation (1985)

This study examined quantitative regional myocardial perfusion (RMP) measured by the washout of 133Xe at rest and after an isoproterenol challenge in 50 patients (group I) studied 8 to 14 days after they underwent saphenous vein bypass grafting to the left coronary artery, and compared this with RMP measured in the native left coronary artery in 14 patients (group II) with significant coronary artery disease and in 12 normal subjects (group III). The double product of the heart rate and aortic systolic pressure was used as an indicator of demand. The statistical significance of group comparisons was analyzed with Dunn's multiple comparisons among means test. Analysis of the data showed no significant difference among the groups with respect to aortic systolic pressure. In subjects at rest, heart rate was lower in groups II and III than in group I, and double product was lower in group II than in group I. After isoproterenol, both heart rate and double product were lower in group II compared with groups I and III, but there was no significant difference between groups I and III with respect to heart rate or double product. Mean resting RMP in group II was lower than in group I; however, results of other group comparisons were insignificant for resting parameters. After isoproterenol, mean flow (ml/100 g/min) in group I was similar to flow in group III (130 +/- 24 vs 139 +/- 26). In contrast, the average flow response after isoproterenol was significantly less in group II when compared with that in group I (105 +/- 20 vs 130 +/- 24) and with that in group III (105 +/- 20 vs 139 +/- 26). Because of differences in levels of demand with isoproterenol, the change in flow was normalized to the percent increase in double product. These data showed results similar to those above, i.e., normalized RMP in patients with coronary artery disease was significantly lower than that in normal subjects (82 +/- 41 vs 119 +/- 57) and in revascularized patients (82 +/- 41 vs 105 +/- 54). However, there was no significant difference between normal subjects and patients who had undergone surgery. To further evaluate the relationship of flow response to demand parameters, we plotted RMP/double product vs resistance. The data revealed a significant correlation between these variables in all groups both in subjects at rest and after isoproterenol.(ABSTRACT TRUNCATED AT 400 WORDS)
Global distribution of atrial ectopic foci triggering recurrence of atrial tachyarrhythmia after electrical cardioversion of long-standing atrial fibrillation: a bi-atrial basket mapping study
Authors: Jiunn-Lee Lin, Ling-Ping Lai, Yung-Zu Tseng, Wen-Pin Lien, Shoei K.Stephen Huang
Journal: Journal of the American College of Cardiology (2001)
Peptide Portions May Hold Key to Amplifying Bone Against Porosis
Authors: Paul Cotton
Journal: JAMA (1990)

PIECES OF PEPTIDES that are encoded in the calcitonin gene may explain enigmas in treatment of bone disease. Amplification of bone formation by two peptides with similar amino acid sequences was reported at the Third International Conference on the Fundamentals of Bone Growth at the University of California, Los Angeles (UCLA), schools of medicine and dentistry. One treatment enigma is that calcitonin regulates normal bone resorption but does not work as well when administered for the treatment of osteoporosis, says Guy Howard, MD, Veterans Administration Medical Center, Miami, Fla. While hormone therapy does work, it has wide-ranging effects like the potential for an increased risk of breast cancer. <i>N</i>-procalcitonin (<i>N</i>-proCT), which is produced by the amino acids that precede those encoded for calcitonin, "may speak to" that enigma, Howard said in presenting the first in vivo results on the new peptide. In vitro, it stimulates proliferation of bone-forming
Some Implications of Illness Behavior for Medical Sampling
Authors: David Mechanic
Journal: New England Journal of Medicine (1963)

AN adequate and representative sample is an important prerequisite for competent studies of etiologic processes in disease. Most medical studies, however, depend largely on populations of sick persons who come to clinics, hospitals and other medical facilities for diagnosis and treatment. Such populations are accessible and convenient, and research based on them is relatively economical. Moreover, the assumption is often made that sampling problems are less acute when basic human processes are being studied. However, to the extent that known clinic and hospital populations are not representative of those having a particular disorder, and to the extent that selection of . . .
Brain Kinetics of Paroxetine and Fluoxetine on the Third Day of Placebo Substitution: A Fluorine MRS Study
Authors: Michael E. Henry, Constance M. Moore, Marc J. Kaufman, David Michelson, Mark E. Schmidt, Eve Stoddard, Alexander J. Vuckevic, Paul J. Berreira, Bruce M. Cohen, Perry F. Renshaw
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: This study tested whether a relationship exists between concentration and response following discontinuation of selective serotonin reuptake inhibitors. METHOD: Eight patients with remitted major depression who were taking 20 mg/day of either fluoxetine or paroxetine underwent placebo substitution for 3 days. Serum drug and brain fluorine levels were obtained before and after placebo substitution. RESULTS: With placebo substitution, a mean of 88% (SD=13%) of brain fluorine signal from fluoxetine (plus fluorinated metabolites) remained, compared with a mean of 38% (SD=17%) of the brain fluorine signal from paroxetine (plus fluorinated metabolites). Among patients taking paroxetine, adverse events during placebo substitution correlated highly with steady-state brain drug levels. CONCLUSIONS: The correlation of clinical effects with brain drug levels in the paroxetine group suggests that relationships between drug response and brain drug concentrations merit further investigation.
Three Pioneers of Canadian Psychiatry
Authors: Cyril Greenland
Journal: JAMA (1967)

For indeed it is one of the lessons of the history of science that each age steps on the shoulders of the ages which have gone before. The value of each age is not its own, but is in part, in large part, a debt to its forerunners. And this age of ours if, like its predecessors, it can boast of something of which it is proud, would could it read the future doubtless find also much of which it would be ashamed.<sup>1</sup>
Marathon Group Therapy and Nonverbal Methods
Authors: IVAN B. GENDZEL
Journal: American Journal of Psychiatry (1970)

The author outlines the structure of a 24-hour encounter group (marathon) meeting. Nonverbal methods were felt to be effective in circumventing verbal barriers, conceptualizing and verbalizing new and unusual experiences, and providing much relevant information. The majority of 100 participants responding to a questionnaire immediately after their marathons felt they had benefited from the experience and that the nonverbal methods had contributed. A follow-up meeting several weeks after the marathon helped to provide closure to the experience.
Cutaneous Sclerosis, Aplastic Anemia, and Antithymocyte Globulin
Authors: Pierre Fenaux
Journal: Annals of Internal Medicine (1989)

Letters and Corrections1 April 1989Cutaneous Sclerosis, Aplastic Anemia, and Antithymocyte GlobulinPierre Fenaux, MD, Stéphane Merignargues, MD, Dominique Pagniez, MD, Anne Janin, MD, Damien Lucidarme, MD, Francis Bauters, MDPierre Fenaux, MDSearch for more papers by this author, Stéphane Merignargues, MDSearch for more papers by this author, Dominique Pagniez, MDSearch for more papers by this author, Anne Janin, MDSearch for more papers by this author, Damien Lucidarme, MDSearch for more papers by this author, Francis Bauters, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-110-7-575_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Balaban and colleagues (1) have reported an unusual case of a patient who had two uncommon clinical findings, cutaneous sclerosis and aplastic anemia. Because both conditions responded to antithymocyte globulin therapy, this therapy may be effective in cutaneous sclerosis. We report a similar case with a different outcome.A 69-year-old woman was referred in September 1987 for pancytopenia, epistaxis, and gingival bleeding. During the previous year, she had the Raynaud phenomenon and increasing tightness of the skin over the abdomen, arms, and thighs. In these areas, the skin was thickened and indurated in large plaques; abnormal pigmentation,...References1. BalabanSheehanLipskyFrenkel ERPE. Treatment of cutaneous sclerosis and aplastic anemia with antithymocyte globulin. Ann Intern Med. 1987;106:56-8. LinkGoogle Scholar2. BonatiAielliCarnevali AFC. Su di un caso di sclerodermia associato ad aplasia midollare globale. Acta Biol Med. 1977;48:499-504. Google Scholar3. MarshGordon Smith JE. The role of antithymocyte globulin in the treatment of chronic acquired bone marrow failure. Blood Rev. 1988;2:141-8. CrossrefMedlineGoogle Scholar4. GluckmanEsperouDevergie EHE. Comparison of cyclosporine A and horse antithymocyte globulin for treatment of severe aplastic anemia: a multicenter prospective randomized trial. Blood. 1988;72: (suppl 1):42a. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Pierre Fenaux, MD; Stéphane Merignargues, MD; Dominique Pagniez, MD; Anne Janin, MD; Damien Lucidarme, MD; Francis Bauters, MDAffiliations: Centre Hospitalier Universitaire 59037 Lille, France PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySevere Aplastic Anemia Associated With Eosinophilic FasciitisA placebo-controlled study on urokinase therapy in systemic sclerosisRecent developments in the therapy of localized and systemic sclerosisSystemic sclerosisTreatment of systemic sclerosis. 1 April 1989Volume 110, Issue 7Page: 575-576KeywordsAplastic anemiaGlobulinsHemorrhage ePublished: 1 December 2008 Issue Published: 1 April 1989 PDF downloadLoading ...
Intravenously Given Ethacrynic Acid and Gastrointestinal Bleeding
Authors: William H. Wilkinson
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Slone et al prior to publication of their "event analysis" of data derived from their surveillance program,<sup>1</sup>graciously reported to these laboratories their suspicion that the intravenous administration of ethacrynic acid is associated with an increased incidence of gastrointestinal bleeding. The opportunity was provided to visit the two hospitals from which these cases were reported. It is our judgment, after reviewing the patients' records, that a number of factors important to consideration of this possible association are controversial, or have been ignored. Slone and colleagues noted an association between ethacrynic acid and gastrointestinal bleeding in 32 patients. Twenty-eight patients' charts were available for review. One was checked out to another department, and three were not provided because the patient was not known by name or hospital number at the record room. This may reflect key punching or other data recording errors. Progress notes, physicians' orders, and
Plasma Renin Concentration in Primary Hyperaldosteronism.
Authors: J. J. Brown
Journal: Annals of Internal Medicine (1968)

s1 May 1968Plasma Renin Concentration in Primary Hyperaldosteronism.J. J. Brown, M.R.C.P., A. F. Lever, M.R.C.P., J. I. S. Robertson, M.R.C.P.J. J. Brown, M.R.C.P.Search for more papers by this author, A. F. Lever, M.R.C.P.Search for more papers by this author, J. I. S. Robertson, M.R.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1152_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is commonly accepted that plasma renin concentration and plasma renin activity is low in patients with primary hyperaldosteronism although the literature includes relatively few cases studied in this way. We report here the results of an analysis of plasma renin concentration in 34 further surgically confirmed cases of this syndrome. In most instances, plasma renin concentration fell below or close to the lower end of the normal range. Plasma renin concentration may increase to values in the upper part of the normal range during acute dietary sodium deprivation and to higher levels during more prolonged treatment with spironolactone. Multiple... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Glasgow, PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1152-1152KeywordsPlasma renin activityPlasma renin concentrationSodium Issue Published: 1 May 1968 PDF DownloadLoading ...
Sildenafil (Viagra) corrects F508-CFTR location in nasal epithelial cells from patients with cystic fibrosis
Authors: R L Dormer
Journal: Thorax (2004)

<b>Background:</b> Most patients with cystic fibrosis (CF) have a ΔF508 mutation resulting in abnormal retention of mutant gene protein (ΔF508-CFTR) within the cell. This study was undertaken to investigate ΔF508-CFTR trafficking in native cells from patients with CF with the aim of discovering pharmacological agents that can move ΔF508-CFTR to its correct location in the apical cell membrane. <b>Method:</b> Nasal epithelial cells were obtained by brushing from individuals with CF. CFTR location was determined using immunofluorescence and confocal imaging in untreated cells and cells treated with sildenafil. The effect of sildenafil treatment on CFTR chloride transport function was measured in CF15 cells using an iodide efflux assay. <b>Results:</b> In most untreated CF cells ΔF508-CFTR was mislocalised within the cell at a site close to the nucleus. Exposure of cells to sildenafil (2 hours at 37°C) resulted in recruitment of ΔF508-CFTR to the apical membrane and the appearance of chloride transport activity. Sildenafil also increased ΔF508-CFTR trafficking in cells from individuals with CF with a single copy ΔF508 (ΔF508/4016ins) or with a newly described CF trafficking mutation (R1283M). <b>Conclusions:</b> The findings provide proof of principle for sildenafil as a ΔF508-CFTR trafficking drug and give encouragement for future testing of sildenafil and related PDE5 inhibitors in patients with CF.
Noninvasive, Repetitive, Quantitative Measurement of Gene Expression from a Bicistronic Message by Positron Emission Tomography, Following Gene Transfer with Adenovirus
Authors: Qianwa Liang, Jeff Gotts, Nagichettiar Satyamurthy, Jorge Barrio, Michael E. Phelps, Sanjiv S. Gambhir, Harvey R. Herschman
Journal: Molecular Therapy (2002)

Gene therapy protocols are hampered by the inability to monitor the location, magnitude, and duration of ectopic gene expression following DNA delivery. Consequently, it is difficult to establish quantitative correlations and/or causal relationships between therapeutic gene expression and phenotypic responses in treated individuals. One approach to monitor "therapeutic gene" expression indirectly is to incorporate reporter genes that can be imaged in vivo into bicistronic transcription units, along with the therapeutic genes. Expression of the dopamine D2 receptor (D2R) and herpes simplex virus thymidine kinase (HSV1-TK) can both be monitored, in vivo, by positron-emission tomography (PET). We created ad.DTm, an adenovirus containing a cytomegalovirus (CMV) early promoter–driven transcription unit, in which the D2R gene is placed proximal to an encephalomyocarditis virus internal ribosomal entry site (IRES) and a modified HSV1-tk gene is placed distal to the IRES. Following intravenous ad.DTm injection into mice, correlated hepatic D2R and HSV1-sr39tk PET reporter gene expression was demonstrated. Repeated microPET scanning quantitated both D2R-dependent sequestration of a positron-emitting ligand and HSV1-TK-dependent sequestration of a positron-emitting product. It is possible, in living mice, to investigate noninvasively and to measure quantitatively and repeatedly correlated expression of two coding regions from a bicistronic transcription unit over a 3-month period following adenovirus delivery.
Mevalonate Kinase Deficiency and Autoinflammatory Disorders
Authors: Dorothea Haas, Georg F. Hoffmann
Journal: New England Journal of Medicine (2007)

A deficiency of mevalonate kinase resulting in mevalonic aciduria was the first inherited defect in cholesterol and nonsterol isoprene biosynthesis to be recognized.1 Nine other enzyme deficiencies have since been identified in the distal part of the cholesterol biosynthesis pathway. They are associated mainly with skeletal and organ malformations, skin abnormalities, and psychomotor retardation. Recently, two defects in the synthesis of coenzyme Q10 (also called ubiquinone) have been associated with disorders that clinically resemble abnormalities of mitochondrial energy metabolism.The clinical manifestations of mevalonic aciduria are diverse.2 Severely affected patients present from birth with failure to thrive, microcephaly, dysmorphic features, . . .
Abstract 4395: Cure of castration-resistant prostate cancer in TRAMP mice by reactivating tumor immunity with a phosphatidylserine-targeting antibody
Authors: Yi Yin, Xianming Huang, Gustavo Barbero, Dan Ye, Philip E. Thorpe
Journal: Cancer Research (2012)

Abstract Androgen deprivation therapy (ADT) is initially effective against prostate cancer, but many patients eventually relapse and die from the outgrowth of castration-resistant disease. Here, we tested the hypothesis that tumor immunity against castration-resistant prostate cancer can be elicited by combining ADT with treatment with a monoclonal antibody that binds exposed phosphatidylserine (PS). The rationale was that PS is an immunosuppressive lipid that becomes exposed on tumor blood vessels and malignant cells in prostate tumors responding to ADT, and inhibits immune responses to prostate tumor antigens. To validate this hypothesis, we castrated TRAMP mice after they had developed prostatic adenocarcinomas and treated them with the PS-targeting antibody, mch1N11. We first demonstrated that PS exposure was induced on tumor vascular endothelium and tumor cells by castration. PS exposure on vessels coincided with regions of hypoxia generated in the tumor microenvironment. Next, we demonstrated that castration combined with treatment with mch1N11 inhibited tumor growth and progression. About half of the treated TRAMP mice did not develop castration-resistant tumors, and eventually died of old age. Immunohistochemical studies revealed that the mch1N11 treatment combined with castration generated T-cell immune responses against TRAMP tumor antigens that kept the tumor in check. Extensive disruption of tumor vasculature and abundant infiltration of immune cells, including CD8 positive T lymphocytes, Natural killer (NK) cells and dendritic cells were observed. Splenocytes from mice treated with mch1N11 plus castration were able to kill TRAMP-C2 specifically in vitro, whereas splenocytes from mice in the other groups could not. These results demonstrate that PS, which becomes exposed on prostate cancer cells and tumor vasculature after ADT, inhibits immunity to TRAMP tumor antigens. Treatment with the PS-targeting antibody mch1N11 reactivates tumor immunity, which can permanently hold new tumor development in check. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4395. doi:1538-7445.AM2012-4395
Oscillating activity of a Ca(2+)-sensitive K+ channel. A prerequisite for migration of transformed Madin-Darby canine kidney focus cells.
Authors: A Schwab, L Wojnowski, K Gabriel, H Oberleithner
Journal: Journal of Clinical Investigation (1994)

Migration plays an important role in the formation of tumor metastases. Nonetheless, little is known about electrophysiological phenomena accompanying or underlying migration. Previously, we had shown that in migrating alkali-transformed Madin-Darby canine kidney focus (MDCK-F) cells a Ca(2+)-sensitive 53-pS K+ channel underlies oscillations of the cell membrane potential. The present study defines the role this channel plays in migration of MDCK-F cells. We monitored migration of individual MDCK-F cells by video imaging techniques. Under control conditions, MDCK-F cells migrated at a rate of 0.90 +/- 0.03 microns/min (n = 201). Application of K+ channel blockers (1 and 5 mmol/liter Ba2+, 5 mmol/liter tetraethylammonium, 100 mumol/liter 4-aminopyridine, 5 nmol/liter charybdotoxin) caused marked inhibition of migration, pointing to the importance of K+ channels in migration. Using patch-clamp techniques, we demonstrated the sensitivity of the Ca(2+)-sensitive 53-pS K+ channel to these blockers. Blockade of this K+ channel and inhibition of migration were closely correlated, indicating the necessity of oscillating K+ channel activity for migration. Migration of MDCK-F cells was also inhibited by furosemide or bumetanide, blockers of the Na+/K+/2Cl- cotransporter. We present a model for migration in which oscillations of cell volume play a central role. Whenever they are impaired, migration is inhibited.
The WHICH? trial: rationale and design of a pragmatic randomized, multicentre comparison of home‐ vs. clinic‐based management of chronic heart failure patients
Authors: Simon Stewart, Melinda J. Carrington, Thomas Marwick, Patricia M. Davidson, Peter Macdonald, John Horowitz, Henry Krum, Phillip J. Newton, Christopher Reid, Paul A. Scuffham
Journal: European Journal of Heart Failure (2011)