tbuckley/cabot-search huggingface dataset:
Obesity and lung function
Authors: D AHMAD
Journal: Thorax (2001)

COPD exacerbationsWe read with interest the paper by Cotton and associates 1 on early discharge for patients with exacerbations of chronic obstructive pulmonary disease and the accompanying editorial by Killen and Ellis. 2 In both publications the 1991 study of our RespiCare home care programme was referenced, 3 and both asserted that our programme was not cost eVective.In fact, our study reached the opposite conclusion-namely, that the Respi-Care programme was shown to be cost eVective.Actual direct care charges in US dollars were used in our calculations of both pre-programme and on-programme costs.Additionally, administrative costs of operating RespiCare were added into the onprogramme costs.Our findings showed that, while hospitalisation costs substantially decreased during the programme, home care costs increased.However, the decrease in hospital costs more than oVset the subsequent increase in home care costs, with a total cost savings of $328 US dollars per patient per month or $3956 per year being realised for those on the RespiCare programme.Although the emphasis of the work was on improvements in clinical outcome, the cost savings were a significant and important aspect of our study.I hope this clarifies any misunderstanding created by the recent articles.
An ex vivo model of severe asthma using reconstituted human bronchial epithelium
Authors: Delphine Gras, Arnaud Bourdin, Isabelle Vachier, Laure de Senneville, Caroline Bonnans, Pascal Chanez
Journal: Journal of Allergy and Clinical Immunology (2012)

Structural changes to the airways are features of severe asthma. The bronchial epithelium facilitates this remodeling process. Learning about the changes that develop in the airway epithelium could improve our understanding of asthma pathogenesis and lead to new therapeutic approaches.We sought to determine the feasibility and relevance of air-liquid interface cultures of bronchial epithelium derived from endobronchial biopsy specimens of patients with different severities of asthma for studying the airway epithelium.Human bronchial epithelial cells derived from endobronchial biopsy specimens of patients with mild and severe asthma were maintained in culture for 21 days in an air-liquid interface to reproduce a fully differentiated airway epithelium. Initially, features of remodeling that included epithelial and subepithelial layers, as well as mucus production, were assessed in paraffin-embedded endobronchial biopsy specimens to evaluate morphologic characteristics of asthmatic patients' epithelia. Ex vivo differentiated epithelia were then analyzed for morphology and function based on ultrastructural analysis, IL-8 release, lipoxin A(4) generation, mucin production, and lipoxygenase gene expression.Morphologic and inflammatory imbalances initially observed in endobronchial biopsy specimens obtained from patients with severe or mild asthma persisted in the air-liquid interface reconstituted epithelium throughout the differentiation process to 21 days. Epithelium from patients with severe asthma produced greater levels of mucin, released more IL-8, and produced lower levels of lipoxin A(4) than that from patients with mild asthma. Expression of 15-lipoxygenase 2 was increased in epithelium from patients with severe asthma, whereas expression levels of MUC5AC, MUC5B, 5-lipoxygenase, and 15-lipoxygeanse 1 were similar to those of patients with mild asthma.Ex vivo cultures of fully differentiated bronchial epithelium from endobronchial biopsy specimens maintain inherent phenotypic differences specifically related to the severity of asthma.
Effect of Potential Confounding Factors on the Thrombolysis in Myocardial Infarction (TIMI) Trial Frame Count and Its Reproducibility
Authors: Adnan Abacı, Abdurrahman Oguzhan, Namık Kemal Eryol, Ali Ergin
Journal: Circulation (1999)

Background —The potential factors that introduce variability into TIMI frame count (TFC) have not been systematically investigated. The goal of this study was to determine if nitrate use, dye injection rate, catheter size, the phase of the cardiac cycle in which dye is injected, or heart rate affect the TFC and to investigate the reproducibility of the TFC. Methods and Results —The dye injection rate was increased 1 mL/s, and angiography was repeated. A coronary angiogram was taken first with an 8F catheter and then with a 6F catheter. After taking angiograms, intracoronary nitrate was given to the patient, and the second angiography was performed. Basal heart rate was increased 20 beats/min, and angiography was repeated. Dye injection was performed at the beginning of systole and diastole. The TFC was not significantly changed by increasing the dye injection rate ( P =0.467) or by changing catheter size ( P =0.693). Nitrate administration significantly increased the TFC from 26.4±11.9 to 32.8±13.3 frames ( P &lt;0.001). Dye injection at the beginning of diastole significantly decreased the TFC from 30.1±8.8 to 24.4±7.9 frames ( P &lt;0.001) for the left coronary artery and from 24.16±4.49 to 21.24±4.45 frames ( P &lt;0.001) for the right coronary artery. Increasing heart rate significantly decreased the TFC from 30.4±6.1 to 25.3±7.2 frames ( P &lt;0.001). Intraobserver and interobserver reproducibility of the TFC was good (mean difference, 1.33±1.24 and 2.57±1.72 frames, respectively). Conclusions —Nitrate use, heart rate, and the phase of the cardiac cycle in which dye is injected had significant effects on the TFC. Therefore, studies comparing TFC need to consider these factors, and the use of nitrates should be either standardized or randomized.
Population-based analysis of the impact and generalizability of the NSABP-B24 study on endocrine therapy for patients with ductal carcinoma in situ of the breast
Authors: A.C. Lo, P.T. Truong, E.S. Wai, A. Nichol, L. Weir, C. Speers, M.M. Hayes, C. Baliski, S. Tyldesley
Journal: Annals of Oncology (2015)
Reasons, considerations, difficulties and documentation of end-of-life decisions in European intensive care units: the ETHICUS Study
Authors: Charles L. Sprung, Thomas Woodcock, Peter Sjokvist, Bara Ricou, Hans-Henrik Bulow, Anne Lippert, Paulo Maia, Simon Cohen, Mario Baras, Seppo Hovilehto, Didier Ledoux, Dermot Phelan, Elisabet Wennberg, Wolfgang Schobersberger
Journal: Intensive Care Medicine (2007)
Corticosteroids in severe pneumonia
Authors: O. Sibila, C. Agustí, A. Torres
Journal: European Respiratory Journal (2008)

The mortality rate in severe community- or hospital-acquired pneumonia is very high, ranging 20–50%. Despite advances in antimicrobial therapy and supportive measures, this rate has not changed in recent years, suggesting that other factors are also responsible for the poor outcome. An abnormal increase in the local and systemic inflammatory response is associated with poor outcome, and this occurs despite adequate antibiotic therapy. There is evidence that acute administration of corticosteroids decreases the inflammatory response and might decrease mortality in severe pneumonia. This has been shown in one small randomised controlled study, terminated prematurely due to 0% mortality in the intervention arm. In addition, an experimental study showed that glucocorticosteroids decrease lung inflammatory response and lung bacterial burden, confirming the results obtained through in vitro investigations. Although these results are promising and suggest a novel role of glucocorticosteroids in pneumonia, the inherent risks and potential side-effects of these drugs require further controlled clinical trials in order to better define the target population before their general use in clinical practice. Specifically, dosage, period of administration, titration, tapering and side-effects are some of the key questions that need to be investigated.
Gene expression endophenotypes: a novel approach for gene discovery in Alzheimer's disease
Authors: Nilüfer Ertekin-Taner
Journal: Molecular Neurodegeneration (2011)

Uncovering the underlying genetic component of any disease is key to the understanding of its pathophysiology and may open new avenues for development of therapeutic strategies and biomarkers. In the past several years, there has been an explosion of genome-wide association studies (GWAS) resulting in the discovery of novel candidate genes conferring risk for complex diseases, including neurodegenerative diseases. Despite this success, there still remains a substantial genetic component for many complex traits and conditions that is unexplained by the GWAS findings. Additionally, in many cases, the mechanism of action of the newly discovered disease risk variants is not inherently obvious. Furthermore, a genetic region with multiple genes may be identified via GWAS, making it difficult to discern the true disease risk gene. Several alternative approaches are proposed to overcome these potential shortcomings of GWAS, including the use of quantitative, biologically relevant phenotypes. Gene expression levels represent an important class of endophenotypes. Genetic linkage and association studies that utilize gene expression levels as endophenotypes determined that the expression levels of many genes are under genetic influence. This led to the postulate that there may exist many genetic variants that confer disease risk via modifying gene expression levels. Results from the handful of genetic studies which assess gene expression level endophenotypes in conjunction with disease risk suggest that this combined phenotype approach may both increase the power for gene discovery and lead to an enhanced understanding of their mode of action. This review summarizes the evidence in support of gene expression levels as promising endophenotypes in the discovery and characterization of novel candidate genes for complex diseases, which may also represent a novel approach in the genetic studies of Alzheimer's and other neurodegenerative diseases.
Short-term variations in oscillatory and spirometric lung function indices among school children
Authors: KL Timonen, JT Randell, RO Salonen, J Pekkanen
Journal: European Respiratory Journal (1997)

The aim of this study was to compare immediate, daily and weekly variation in respiratory resistance measured by means of the forced oscillation technique (Rrs,FOT) to spirometric indices in 7-12 year old children with chronic respiratory symptoms. The lung function measurements were performed in 19 children on 4 days, i.e. two consecutive days during two consecutive weeks. On each day, the measurements were carried out at the same time of day and always repeated three times. In addition, Rrs,FOT and spirometric lung function indices were compared with an exercise challenge test in 12 children. Intrasubject coefficients of variation (CoVs) for Rrs,FOT were larger than those for spirometric indices. Only in the immediately repeated measurements was the CoV of maximal expiratory flow at 25% vital capacity larger than that of Rrs,FOT (16.6 vs 14.9%). At all time intervals, the smallest CoVs were observed in forced vital capacity (FVC) or in the ratio of forced expiratory volume in one second to FVC (2.0-2.6%). When excluding Rrs,FOT values which were not within 2 SD (0.11 kPa.L-1.s) of the differences between the immediately repeated measurements, the CoV of the immediately repeated measurements of Rrs,FOT was reduced to 9.1%, being smaller than that of maximal mid-expiratory flow (10.1%). However, even then the day-to-day variation in Rrs,FOT was clearly larger (16.0%) than those of the airflow indices at specified lung volumes (7.2-8.3%). This was also true for the weekly variation. In the exercise challenge test, there were larger changes in Rrs,FOT values than in the spirometric indices, but Rrs,FOT was the most sensitive index to detect changes in the respiratory system. In conclusion, the variation in Rrs,FOT values was larger than that of most spirometric indices. When a reliability index was applied, the immediate variation in Rrs,FOT values was comparable to those of the airflow indices at specified lung volumes. Rrs,FOT was also the most sensitive index in the exercise challenge test, and therefore it seems to be suitable for detection of short-term functional changes in the respiratory system. However, the relatively low repeatability of Rrs,FOT over days and weeks may limit its applicability to longer-term follow-ups.
A new I subregion (I-J) marked by a locus (Ia-4) controlling surface determinants on suppressor T lymphocytes.
Authors: D B Murphy, L A Herzenberg, K Okumura, L A Herzenberg, H O McDevitt
Journal: The Journal of Experimental Medicine (1976)

In an accompanying publication we show that a subpopulation of T lymphocytes, which includes allotype suppressor T cells, selectively expresses I-region determinants. In this report, we show that these determinants are controlled by a new locus, Ia-4. Unlike the classically defined Ia antigens, they are not found on B lymphocytes. Antibody against Ia-4 determinants cannot be detected by conventional dye exclusion cytoxicity assays, suggesting that they are present on a small subpopulation (less than 10%) of peripheral T lymphocytes. The Ia-4 locus marks a new I subregion, provisionally designated I-J. This chromosomal segment is defined by the crossover positions in strains B10.A(5R) (K-end boundary) and B10.HTT (D-end boundary), and maps between the I-B and I-C subregions.
Molecular characterization of angiotensin II--induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype.
Authors: J Sadoshima, S Izumo
Journal: Circulation Research (1993)

Increasing evidence suggests that angiotensin II (Ang II) may act as a growth factor for the heart. However, direct effects of Ang II on mammalian cardiac cells (myocytes and nonmyocytes), independent of secondary hemodynamic and neurohumoral effects, have not been well characterized. Therefore, we analyzed the molecular phenotype of cultured cardiac cells from neonatal rats in response to Ang II. In addition, we examined the effects of selective Ang II receptor subtype antagonists in mediating the biological effects of Ang II. In myocyte culture, Ang II caused an increase in protein synthesis without changing the rate of DNA synthesis. In contrast, Ang II induced increases in protein synthesis, DNA synthesis, and cell number in nonmyocyte cultures (mostly cardiac fibroblasts). The Ang II-induced hypertrophic response of myocytes and mitogenic response of fibroblasts were mediated primarily by the AT1 receptor. Ang II caused a rapid induction of many immediate-early genes (c-fos, c-jun, jun B, Egr-1, and c-myc) in myocyte and nonmyocyte cultures. Ang II induced "late" markers for cardiac hypertrophy, skeletal alpha-actin and atrial natriuretic factor expression, within 6 hours in myocytes. Ang II also caused upregulation of the angiotensinogen gene and transforming growth factor-beta 1 gene within 6 hours. Induction of immediate-early genes, late genes, and growth factor genes by Ang II was fully blocked by an AT1 receptor antagonist but not by an AT2 receptor antagonist. These results indicate that: (1) Ang II causes hypertrophy of cardiac myocytes and mitogenesis of cardiac fibroblasts, (2) the phenotypic changes of cardiac cells in response to Ang II in vitro closely mimic those of growth factor response in vitro and of load-induced hypertrophy in vivo, (3) all biological effects of Ang II examined here are mediated primarily by the AT1 receptor subtype, and (4) Ang II may initiate a positive-feedback regulation of cardiac hypertrophic response by inducing the angiotensinogen gene and transforming growth factor-beta 1 gene.
Home Medical Testing Expands, Utility Still Being Explored
Authors: Wendy J. Meyeroff
Journal: Annals of Internal Medicine (1997)

Currents15 October 1997Home Medical Testing Expands, Utility Still Being ExploredWendy J. MeyeroffWendy J. MeyeroffSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-8_Part_1-199710150-00044 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Not long ago, the only medical test that patients could use at home was a thermometer. Then in the 1960s, urine tests to measure blood glucose levels became available for home use; in 1976, the first home pregnancy test kit was issued. Today, patients can, among other things, measure their cholesterol, determine a child's paternity, or detect HIV infection.Steven Gutman, MD, director of the U.S. Food and Drug Administration's (FDA) division of clinical laboratory devices, said that an even broader range of home tests is on the horizon. “Technology is moving like lightning, and a wide range of analytes ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 October 1997Volume 127, Issue 8_Part_1Page: 663-664 Issue Published: 15 October 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Accumulation of PiZ alpha 1-antitrypsin causes liver damage in transgenic mice.
Authors: J A Carlson, B B Rogers, R N Sifers, M J Finegold, S M Clift, F J DeMayo, D W Bullock, S L Woo
Journal: Journal of Clinical Investigation (1989)

Circulating alpha 1-antitrypsin is synthesized primarily in the liver and secreted into the bloodstream, where it serves as the major protease inhibitor. The PiZ variant of alpha 1-antitrypsin is associated with decreased levels of the protein in sera as a result of its retention within hepatocytes. Homozygosity for the variant allele predisposes individuals to the development of pulmonary emphysema and an increased risk for liver disease. We and others have previously demonstrated that the normal PiM human alpha 1-antitrypsin gene can be properly expressed in the livers of transgenic mice. The PiZ variant of the human alpha 1-antitrypsin gene was introduced into the germline of mice to determine whether the mutant protein would accumulate in mouse hepatocytes and if such accumulation would result in the development of liver damage in an animal model. As expected, the mutant human protein was abundantly synthesized in the livers of the transgenic animals and accumulated within the rough endoplasmic reticulum of hepatocytes as it does in human patients. PiZ mice developed significantly more liver necrosis and inflammation than PiM transgenic mice or control littermates. The degree of liver damage was correlated with the amount of PiZ alpha 1-antitrypsin accumulated in the liver of the different pedigrees of mice. Although 40% of PiZ mice tested were seropositive for mouse hepatitis virus (MHV), the degree of liver damage was not influenced by the MHV seropositivity; rather, it was related only to the presence of accumulated PiZ protein.
Incidence and evolution of oxaliplatin-induced peripheral sensory neuropathy in diabetic patients with colorectal cancer: a pooled analysis of three phase III studies
Authors: R.K. Ramanathan, M.L. Rothenberg, A. de Gramont, C. Tournigand, R.M. Goldberg, S. Gupta, T. André
Journal: Annals of Oncology (2009)
Experimental Abdominal Aortic Aneurysm Formation Is Mediated by IL-17 and Attenuated by Mesenchymal Stem Cell Treatment
Authors: Ashish K. Sharma, Guanyi Lu, Andrea Jester, William F. Johnston, Yunge Zhao, Vanessa A. Hajzus, M. Reza Saadatzadeh, Gang Su, Castigliano M. Bhamidipati, Gaurav S. Mehta, Irving L. Kron, Victor E. Laubach, Michael P. Murphy, Gorav Ailawadi, Gilbert R. Upchurch
Journal: Circulation (2012)

Background— Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, smooth muscle activation and matrix degradation. This study tests the hypothesis that CD4+ T-cell–produced IL-17 modulates inflammation and smooth muscle cell activation, leading to the pathogenesis of AAA and that human mesenchymal stem cell (MSC) treatment can attenuate IL-17 production and AAA formation. Methods and Results— Human aortic tissue demonstrated a significant increase in IL-17 and IL-23 expression in AAA patients compared with control subjects as analyzed by RT-PCR and ELISA. AAA formation was assessed in C57BL/6 (wild-type; WT), IL-23 −/− or IL-17 −/− mice using an elastase-perfusion model. Heat-inactivated elastase was used as control. On days 3, 7, and 14 after perfusion, abdominal aorta diameter was measured by video micrometry, and aortic tissue was analyzed for cytokines, cell counts, and IL-17–producing CD4+ T cells. Aortic diameter and cytokine production (MCP-1, RANTES, KC, TNF-α, MIP-1α, and IFN-γ) was significantly attenuated in elastase-perfused IL-17 −/− and IL-23 −/− mice compared with WT mice on day 14. Cellular infiltration (especially IL-17–producing CD4+ T cells) was significantly attenuated in elastase-perfused IL-17 −/− mice compared with WT mice on day 14. Primary aortic smooth muscle cells were significantly activated by elastase or IL-17 treatment. Furthermore, MSC treatment significantly attenuated AAA formation and IL-17 production in elastase-perfused WT mice. Conclusions— These results demonstrate that CD4+ T-cell–produced IL-17 plays a critical role in promoting inflammation during AAA formation and that immunomodulation of IL-17 by MSCs can offer protection against AAA formation.
Extent of Pelvic Lymph Node Dissection and the Impact of Standard Template Dissection on Nomogram Prediction of Lymph Node Involvement
Authors: Guilherme Godoy, Kian Tai Chong, Angel Cronin, Andrew Vickers, Vincent Laudone, Karim Touijer, Bertrand Guillonneau, James A. Eastham, Peter T. Scardino, Jonathan A. Coleman
Journal: European Urology (2011)
Pentosan polysulfate‐induced thrombocytopenia and thrombosis
Authors: Brigitte Tardy‐Poncet, Bernard Tardy, Françoise Grelac, Jacqueline Reynaud, Patrick Mismetti, Jean Claude Bertrand, Denis Guyotat
Journal: American Journal of Hematology (1994)

Abstract Pentosan polysulfate is a low‐molecular‐weight sulfated polysaccharide used as an antithrombotic drug. We present two patients who developed thrombocytopenia and venous thrombosis during treatment with pentosan polysulfate. The relationship between pentosan polysulfate and thrombocytopenia is supported by platelet aggregation and serotonin release tests. In the light of the literature and our two cases, it appears that pentosan polysulfate alone as standard heparin and low‐molecular‐weight heparin can induce thrombocytopenia and thrombosis. Platelet counts should therefore be periodically monitored during pentosan polysulfate treatment. In the case of pentosan polysulfate‐induced thrombocytopenia, it seems that heparin or low‐molecular‐weight heparin should not be instituted during the acute phase even it platelet aggregation studies are negative, because of their low sensitivity. After remission of thrombocytopenia, whether or not glycoaminoglycans can be reinstituted, at least temporarily, after antibody had disappeared is still an open question. © 1994 Wiley‐Liss, Inc.