tbuckley/cabot-search huggingface dataset:
Outcome of Hospitalized Injured Patients After Institution of a Trauma System in an Urban Area
Authors: R J Mullins, J Veum-Stone, M Helfand, M Zimmer-Gembeck, J R Hedges, P A Southard, D D Trunkey
Journal: JAMA (1994)

To determine if risk of death for hospitalized injured patients changes when an urban trauma system is implemented.An analysis of the risk of death in hospitalized injured patients in 1984 and 1985 (pretrauma system), 1986 and 1987 (early trauma system), and 1990 and 1991 (established trauma system) using hospital discharge abstract data.A total of 18 acute care hospitals in the four-county area encompassing Portland, Ore.A cohort of 70,350 hospitalized patients with at least one discharge diagnosis indicating injury.Death during hospitalization.After the trauma system was established, 77% of patients in the region with an Injury Severity Score (ISS) of 16 or greater were admitted to level I trauma centers. More than 72% of patients with an ISS less than 16 were hospitalized in nontrauma centers. Risk of death for injured patients hospitalized at level I trauma centers declined after the trauma system was established (odds ratio, 0.65; 95% confidence interval, 0.51 to 0.81). Patients who died in trauma centers after institution of the trauma system were younger and had more severe injuries, and the majority died within 1 day of admission, whereas patients who died in nontrauma centers died a median of 5 days after admission.Establishment of a trauma system shifted the more seriously injured patients to level I trauma centers, where there was a significant reduction in the adjusted death rate.
Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche
Authors: Yanming Bi, Driss Ehirchiou, Tina M Kilts, Colette A Inkson, Mildred C Embree, Wataru Sonoyama, Li Li, Arabella I Leet, Byoung-Moo Seo, Li Zhang, Songtao Shi, Marian F Young
Journal: Nature Medicine (2007)
Galectin-3 is induced in rheumatoid arthritis synovial fibroblasts after adhesion to cartilage oligomeric matrix protein
Authors: M Neidhart
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Galectin-3 is expressed in the synovial tissue of patients with rheumatoid arthritis (RA), particularly at sites of joint destruction. <b>Objective:</b> To explore the possibilities that galectin-3 is induced either by proinflammatory cytokines or by adhesion to cartilage components. <b>Methods:</b> Cell culture plates were coated with fibronectin, collagens I–VI, or cartilage oligomeric matrix protein (COMP), and the suspended cells were then added. The medium was changed after 1 hour at 37°C. Adherent cells were further incubated for 18 hours in the presence or absence of tumour necrosis factor α (TNFα) or interleukin 1β. Cells were pretreated with murine IgG1, anti-CD29, -CD51, -CD61 (integrins), or -CD3 monoclonal antibodies and transferred to culture plates coated with COMP. Adherent cells were counted by light microscopy. The expression of intracellular galectin-3, or cell surface CD29, CD51, and CD61 was determined by flow cytometry before and after adhesion. <b>Results:</b> Four times more RA synovial fibroblasts (SF) than osteoarthritis SF adhered to COMP. RA SF presented more cell surface integrins, and monoclonal antibodies against CD51 inhibited the adhesion to COMP by 80%. TNFα reduced the expression of CD61 and the adhesion to COMP, but did not reverse the adhesion once it had taken place. The adhesion of RA SF to COMP was found to increase the intracellular level of galectin-3. In contrast, intracellular galectin-3 decreased after exposure to TNFα. <b>Conclusion:</b> The increase of galectin-3 occurs after adhesion to COMP, and the αVβ3 receptor (CD51/CD61) has a pivotal role in this process.
Quality-of-Life Measurement in Randomized Clinical Trials in Breast Cancer: An Updated Systematic Review (2001–2009)
Authors: Julie Lemieux, Pamela J. Goodwin, Louise J. Bordeleau, Sophie Lauzier, Valérie Théberge
Journal: JNCI Journal of the National Cancer Institute (2011)

Quality-of-life (QOL) measurement is often incorporated into randomized clinical trials in breast cancer. The objectives of this systematic review were to assess the incremental effect of QOL measurement in addition to traditional endpoints (such as disease-free survival or toxic effects) on clinical decision making and to describe the extent of QOL reporting in randomized clinical trials of breast cancer.We conducted a search of MEDLINE for English-language articles published between May-June 2001 and October 2009 that reported: 1) a randomized clinical trial of breast cancer treatment (excluding prevention trials), including surgery, chemotherapy, hormone therapy, symptom control, follow-up, and psychosocial intervention; 2) the use of a patient self-report measure that examined general QOL, cancer-specific or breast cancer-specific QOL or psychosocial variables; and 3) documentation of QOL outcomes. All selected trials were evaluated by two reviewers, and data were extracted using a standardized form for each variable. Data are presented in descriptive table formats.A total of 190 randomized clinical trials were included in this review. The two most commonly used questionnaires were the European Organization for Research and Treatment of Cancer QOL Questionnaire and the Functional Assessment of Cancer Therapy/Functional Assessment of Chronic Illness Therapy. More than 80% of the included trials reported the name(s) of the instrument(s), trial and QOL sample sizes, the timing of QOL assessment, and the statistical method. Statistical power for QOL was reported in 19.4% of the biomedical intervention trials and in 29.9% of the nonbiomedical intervention trials. The percentage of trials in which QOL findings influenced clinical decision making increased from 15.2% in the previous review to 30.1% in this updated review for trials of biomedical interventions but decreased from 95.0% to 63.2% for trials of nonbiomedical interventions. Discordance between reviewers ranged from 1.1% for description of the statistical method (yes vs no) to 19.9% for the sample size for QOL.Reporting of QOL methodology could be improved.
Long term prognosis of Crohn's disease with onset in childhood and adolescence.
Authors: J Puntis, A S McNeish, R N Allan
Journal: Gut (1984)

The long term outcome has been determined in 67 children with Crohn9s disease whose symptoms started at or before 16 years of age. The mean period of follow up was 15.0 years (range 1.5-47 years). The number of children diagnosed in each quinquennium has not increased. Nearly all patients had gastrointestinal symptoms at presentation, but in some cases these were only elicited on careful enquiry. Only four children presented with growth retardation alone. Twenty one per cent of the children had diffuse small bowel disease at onset or during the period of review and posed major problems in management with high morbidity and mortality. They were generally treated medically to suppress disease activity and surgical intervention was restricted to resection of local stricture formation. The outcome in distal ileal +/- right colonic disease was similar to that in the adult. Patients with colonic disease (27% of total) were treated medically but 83% required surgical resection after a mean interval of only four years (range 0-9 years). Growth failure occurred in 21 children (height and weight less than 3rd centile) and 11 of these had a period of catch up growth; 10 after resection (ileal +/- right colon resected, eight; colonic resection, two) and one after medical treatment. Ten have permanent growth and height retardation, of whom four had diffuse small bowel disease and three had early recurrence after surgical resection. Nine children have died during the period of review, of whom six had diffuse small bowel disease. Despite the high morbidity, 38 of the 58 survivors are now well with no evidence of recurrent disease. A further 14 are well, but with radiological evidence of residual (colon, three; diffuse small bowel, eight) or recurrent (three) disease. Only six have symptomatic disease at present.
The Programmed Death-1 (PD-1) Pathway Regulates Autoimmune Diabetes in Nonobese Diabetic (NOD) Mice
Authors: Mohammed Javeed I. Ansari, Alan D. Salama, Tanuja Chitnis, R. Neal Smith, Hideo Yagita, Hisaya Akiba, Tomohide Yamazaki, Miyuki Azuma, Hideyuki Iwai, Samia J. Khoury, Hugh Auchincloss, Mohamed H. Sayegh
Journal: The Journal of Experimental Medicine (2003)

Programmed death-1 (PD-1) receptor, an inhibitory costimulatory molecule found on activated T cells, has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. We investigated the role of this pathway in the development of autoimmune diabetes. PD-1 or PD-L1 but not PD-L2 blockade rapidly precipitated diabetes in prediabetic female nonobese diabetic (NOD) mice regardless of age (from 1 to 10-wk-old), although it was most pronounced in the older mice. By contrast, cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) blockade induced disease only in neonates. Male NOD mice also developed diabetes after PD-1–PD-L1 pathway blockade, but NOR mice, congenic to NOD but resistant to the development of diabetes, did not. Insulitis scores were significantly higher and frequency of interferon γ–producing GAD-reactive splenocytes was increased after PD-1–PD-L1 pathway blockade compared with controls. Interestingly, PD-L1 but not PD-L2 was found to be expressed on inflamed islets of NOD mice. These data demonstrate a central role for PD-1–PD-L1 interaction in the regulation of induction and progression of autoimmune diabetes in the NOD mouse and provide the rationale to develop new therapies to target this costimulatory pathway in this disease.
Limited effect of clarithromycin in non-elderly, non-severe patients with influenza
Authors: Hiroshi Ishii, Kosaku Komiya, Hisako Kushima, Hiroaki Oka, Hiroshi Mukae, Jun-ichi Kadota
Journal: European Respiratory Journal (2012)

Background: Macrolides, including clarithromycin, are molecules with antibacterial activity that also have anti-inflammatory properties. They have been reported to have inhibitory effects on influenza virus infection.

Objective: To determine the effect of concurrent therapy of clarithromycin and neuraminidase inhibitors for influenza on an outpatient clinic basis.

Method: This was an open-label study involving several hospitals in Japan. The clinical episodes of 141 non-immunosuppressed outpatients with seasonal influenza A (2010-2011), including 67 patients treated with a neuraminidase inhibitor alone and 74 treated with the combination therapy (mean age: 30 and 31 years, respectively), were analyzed.

Result: There was no additional efficacy when clarithromycin was used in combination with the neuraminidase inhibitor with regard to the duration of fever, cough, nasal secretions, or general malaise. However, the duration of cough in patients without cough at the onset was significantly shortened by the combined treatment compared to the treatment with the anti-influenza drug alone.

Conclusion: Although the effect of clarithromycin in non-elderly patients with seasonal influenza A was limited, further studies might be needed to determine the additional or preventive effect of clarithromycin during influenza virus infection for elderly subjects or patients complicated with serious underlying diseases.
Design Strategies for Longitudinal Spirometry Studies
Authors: MEI-LIN WANG, ERDOGAN GUNEL, EDWARD L. PETSONK
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Measuring the longitudinal change in FEV1 is useful for assessing the adverse effects of respiratory exposures and pulmonary diseases. Investigators seek to estimate the "true" mean FEV1 slope ( μβ) of an infinite population. The difference between the estimated mean FEV1 slope (^μ β) and the true mean slope, resulting from biological variation and measurement errors, can be minimized by increasing the number of subjects (N), years of follow-up (D), or the frequency of measurements (P). We defined maximum error emax such that P[ ‖μ̌β − μβ‖ ⩽ emax] = 0.95, and thus emax is one-half the width of the 95% confidence interval for μβ. We computed the values of emax on the basis of actual data obtained from 160 coal miners and working nonminers who had completed 11 spirometry measurements, using recommended equipment and procedures, at 6-mo intervals over 5 yr. Individual 5-yr FEV1 slopes ( Δ FEV1) were calculated by linear regression. For a range of values of N, D, and P, tables are provided for emax, the magnitude of detectable differences in Δ FEV1 between two groups, and the recommended number of subjects needed in each of two groups to reliably detect the anticipated differences in Δ FEV1. The tables provide unique guidance for investigators in selecting among various study design options.
Immunologic differentiation of classic hemophilia (factor VIII deficiency) and von Willebrand's disease
Authors: Theodore S. Zimmerman, Oscar D. Ratnoff, Arnold E. Powell
Journal: Journal of Clinical Investigation (1971)

Heterologous antiserum was prepared in rabbits against highly purified human antihemophilic factor (AHF, factor VIII). This antiserum blocked the clot-promoting properties of AHF and, when suitably absorbed, formed a single precipitin line against AHF upon immunoelectrophoresis. Material antigenically similar to normal AHF was detected in normal amounts in plasma concentrates in each of 22 patients with classic hemophilia, in a patient with an acquired circulating anticoagulant against AHF, and in a patient with deficiencies both of AHF and proaccelerin (factor V). AHF-like antigen was present in normal human serum. In contrast, material antigenically related to AHF was found in decreased amounts in the concentrates prepared from the plasma of 11 patients with von Willebrand's disease. The experiments described suggest that von Willebrand's disease is a disorder in which a true deficiency of AHF exists. Whether the AHF-like material found in classic hemophilia is nonfunctional through a defect in structure or through the intervention of an inhibitor has not been shown.
Transcriptional regulation of FGF-2 gene expression in cardiac myocytes
Authors: S JIMENEZ
Journal: Cardiovascular Research (2004)

Objective: Fibroblast growth factor-2 (FGF-2) exerts its cardioprotective effect through cell surface receptor signaling and may play a role in the normal maintenance of a healthy myocardium. One mechanism of FGF-2 release from contracting cardiomyocytes is through transient sarcolemmal disruption, with accumulation in the extracellular matrix. Continuous FGF-2 release would require a link to synthesis and, thus, we examined regulation of FGF-2 promoter activity in cardiomyocytes as a potential target for optimizing cardioprotection. Methods and results: To investigate autoregulation, neonatal rat cardiomyocytes, (NRCM), were transfected with ∼1 or 0.1 kb of rat FGF-2 promoter sequences linked to luciferase, −1058FGF–2p.luc and −110FGF–2p.luc, and treated with or without FGF-2. FGF-2 promoter activity was significantly increased ∼2.5-fold with both genes. The proximal promoter region of rat FGF-2 contains putative binding sites for the early growth response-1 (Egr-1) and stimulating protein 1 (Sp1) transcription factors. Overexpression of Egr-1 and Sp1 increased −1058FGF–2p.luc expression by 4.4- and 8.7-fold, respectively. Mutation of Egr-1 and overlapping Sp1 sites did not blunt the response of −110FGF–2p.luc to FGF-2 treatment but did significantly reduce basal promoter activity. Transgenic mice expressing −1058FGF–2p.luc were treated with isoproterenol (IsP) to increase heart rate and endogenous FGF-2 release. FGF-2 promoter activity was stimulated significantly at 6 h, and increases in both FGF-2 and its receptor mRNA levels were also detected. In contrast, no effect of IsP was seen on −1058FGF–2p.luc or −110FGF–2p.luc in transfected NRCMs. Conclusions: FGF-2 released from cardiomyocytes may act to regulate its own synthesis at the transcriptional level. The mechanism does not appear to require an intact Egr-1 site in the proximal promoter region. This may, however, reflect redundancy in the control of FGF-2 promoter activity as our data support a stimulatory role for Egr-1 and Sp1.
Increased airway iron as a potential factor in the persistence of Pseudomonas aeruginosa infection in cystic fibrosis
Authors: D. W. Reid, V. Carroll, C. O'May, A. Champion, S. M. Kirov
Journal: European Respiratory Journal (2007)

Iron availability is critical to many bacteria and increased iron has been described in airway secretions in cystic fibrosis (CF). The main aim of the present study was to assess the relationship between iron in CF sputum and the quantitative bacterial burden. Iron, ferritin and total cell counts (TCC) were assessed in sputum samples obtained from 15 clinically stable CF patients chronically infected with Pseudomonas aeruginosa . Sputum samples were also obtained at the commencement of episodes of acute exacerbation in 10 subjects and analyses were repeated in six of these exacerbation cases after i.v. antibiotic treatment. The relationship between iron indices and the presence of P. aeruginosa , as well as total anaerobic bacterial load, was determined. Sputum was also obtained from 10 CF patients with no evidence of infection with P. aeruginosa and 11 normal healthy controls. Sputum iron, ferritin and TCC were significantly elevated in all CF patients, even in those not infected with P. aeruginosa , compared with healthy controls. There was a strong positive relationship between sputum iron and P. aeruginosa in clinically stable patients, but not in samples obtained during an acute exacerbation. There was no relationship between sputum iron and anaerobic bacterial load. Antibiotic treatment significantly reduced sputum TCC and anaerobic bacterial load, but not iron, ferritin or the presence of P. aeruginosa during an exacerbation. In conclusion, the present study suggests that increased airway iron may be important to Pseudomonas aeruginosa persistence in cystic fibrosis.
Spermatogonial stem cells: questions, models and perspectives
Authors: Jens Ehmcke, Joachim Wistuba, Stefan Schlatt
Journal: Human Reproduction Update (2006)

This review looks into the phylogeny of spermatogonial stem cells and describes their basic biological features. We are focusing on species-specific differences of spermatogonial stem cell physiology. We propose revised models for the clonal expansion of spermatogonia and for the potential existence of true stem cells and progenitors in primates but not in rodents. We create a new model for the species-specific arrangements of spermatogenic stages which may depend on the variable clonal expansion patterns. We also provide a brief overview of germ cell transplantation as a powerful tool for basic research and its potential use in a clinical setting.
Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes
Authors: Bruno Ledergerber, Jens D Lundgren, A Sarah Walker, Caroline Sabin, Amy Justice, Peter Reiss, Cristina Mussini, Ferdinand Wit, Antonella d'Arminio Monforte, Rainer Weber, Gregory Fusco, Schlomo Staszewski, Matthew Law, Robert Hogg, Fiona Lampe, M John Gill, Francesco Castelli, Andrew N Phillips
Journal: The Lancet (2004)
Electroaugmentation of Ventricular Performance and Oxygen Consumption by Repetitive Application of Paired Electrical Stimuli
Authors: JOHN ROSS, EDMUND H. SONNENBLICK, GERARD A. KAISER, PETER L. FROMMER, EUGENE BRAUNWALD
Journal: Circulation Research (1965)

When a depolarizing stimulus is delivered to the ventricle immediately following the refractory period, little extrasystolic contraction occurs and repetitive paired stimulation then results in a marked and sustained improvement of ventricular performance which has been termed electroaugmentation. The present study characterizes this augmentation and its effects on myocardial oxygen consumption (MV O O 2 ). In 45 experiments on 14 dogs in which mean aortic pressure and stroke volume were held constant by right heart bypass, a change from single to paired stimulation at identical contraction rates markedly increased the performance of the left ventricle as evidenced by shortening of ejection time increase in left ventricular dp/dt, stroke power, and peak ejection rate, and sometimes a fall in end diastolic pressure. Similar resul were obtained after administration of resepine or nethalide. In 15 experiments on 11 dogs the stroke volume of the left ventricle was varied during single and paired stimulation. Improvement in left ventricular performance during paired stimulation was always evidenced by increased speed of contractic and an upward displacement of the curvesrelating end diastolic pressure to stroke powe mean and peak ejection rates, and some times by an upward displacement of the curves relating end diastolic pressure to stroke volume and stroke work. In eight experiments MV · O O 2 was determined during single and paired stimulation, stroke volume, mean aortic pressure, and contraction rate being held constant. Paired stimulation always increased MV · O O 2 the average increase being 35%. Despite the rise in MV · O O 2 , a reduction in the tension-time index always occurred. These studies indicate that repetitive paired stimulation exerts a powerful and sustained positive inotropic in fluence on the mammalian ventricle and that at a relatively constant level of external world the increased velocity of ventricular contraction which accompanies this effect results in an increase in MV · O O 2 .
Plasminogen-activator-inhibitor-1 4G/5G promoter polymorphism and prognosis of severely injured patients
Authors: Thilo Menges, Peter WM Hermans, Simon G Little, Tanja Langefeld, Olav Böning, Jörg Engel, Marcel Sluijter, Ronald de Groot, Gunter Hempelmann
Journal: The Lancet (2001)
Cytokines in asthma
Authors: J.C. Kips
Journal: European Respiratory Journal (2001)

The airway inflammation underlying asthma is regulated by a network of mutually interacting cytokines. The exact functional role of each individual cytokine in the pathogenesis of the disease remains to be fully established. Type 2 T‐helper cells are currently considered to play a crucial role in this process. In vivo animal data suggest a sequential involvement of interleukin (IL)‐4 and IL‐5 in the induction of allergen-induced airway changes. The potential role of other type 2 T‐helper cell-like cytokines in asthma is increasingly being recognized. In particular, IL‐4 and -13 display a large degree of redundancy. Whereas IL‐4 seems to be crucial in the primary allergen sensitization process, IL-13 might be more important during secondary exposure to aerosolized allergen. Animal models also indicate that T‐cell-derived cytokine production, rather than eosinophil influx or immunoglobulin‐E synthesis, is causally related to altered airway behaviour. An important aspect when evaluating the functional role of cytokines in a complex disease such as asthma is the interaction with other cytokines in the microenvironment. Increased expression of pro-inflammatory cytokines such as tumour necrosis factor‐α can further enhance the inflammatory process, and is increasingly linked to disease severity. In addition, decreased expression of immunoregulatory cytokines, including interleukin-12, interleukin-18 or interferon gamma could also strengthen the type 2 T‐helper cell-driven inflammatory process.