tbuckley/cabot-search huggingface dataset:
The Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity Index in Chronic Obstructive Pulmonary Disease
Authors: Bartolome R. Celli, Claudia G. Cote, Jose M. Marin, Ciro Casanova, Maria Montes de Oca, Reina A. Mendez, Victor Pinto Plata, Howard J. Cabral
Journal: New England Journal of Medicine (2004)

Chronic obstructive pulmonary disease (COPD) is characterized by an incompletely reversible limitation in airflow. A physiological variable--the forced expiratory volume in one second (FEV1)--is often used to grade the severity of COPD. However, patients with COPD have systemic manifestations that are not reflected by the FEV1. We hypothesized that a multidimensional grading system that assessed the respiratory and systemic expressions of COPD would better categorize and predict outcome in these patients.We first evaluated 207 patients and found that four factors predicted the risk of death in this cohort: the body-mass index (B), the degree of airflow obstruction (O) and dyspnea (D), and exercise capacity (E), measured by the six-minute-walk test. We used these variables to construct the BODE index, a multidimensional 10-point scale in which higher scores indicate a higher risk of death. We then prospectively validated the index in a cohort of 625 patients, with death from any cause and from respiratory causes as the outcome variables.There were 25 deaths among the first 207 patients and 162 deaths (26 percent) in the validation cohort. Sixty-one percent of the deaths in the validation cohort were due to respiratory insufficiency, 14 percent to myocardial infarction, 12 percent to lung cancer, and 13 percent to other causes. Patients with higher BODE scores were at higher risk for death; the hazard ratio for death from any cause per one-point increase in the BODE score was 1.34 (95 percent confidence interval, 1.26 to 1.42; P<0.001), and the hazard ratio for death from respiratory causes was 1.62 (95 percent confidence interval, 1.48 to 1.77; P<0.001). The C statistic for the ability of the BODE index to predict the risk of death was larger than that for the FEV1 (0.74 vs. 0.65).The BODE index, a simple multidimensional grading system, is better than the FEV1 at predicting the risk of death from any cause and from respiratory causes among patients with COPD.
Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis
Authors: Xiaoling Qiang, Weng-Lang Yang, Rongqian Wu, Mian Zhou, Asha Jacob, Weifeng Dong, Michael Kuncewitch, Youxin Ji, Huan Yang, Haichao Wang, Jun Fujita, Jeffrey Nicastro, Gene F Coppa, Kevin J Tracey, Ping Wang
Journal: Nature Medicine (2013)
Quantifying comorbidity in individuals with COPD: a population study
Authors: Andrea S. Gershon, Graham C. Mecredy, Jun Guan, J. Charles Victor, Roger Goldstein, Teresa To
Journal: European Respiratory Journal (2014)

Chronic obstructive pulmonary disease (COPD) has been associated with many types of comorbidity. We aimed to quantify the real world impact of COPD on lower respiratory tract infection, cardiovascular disease, diabetes, psychiatric disease, musculoskeletal disease and cancer, and their impact on COPD through health services. A population study using health administrative data from Ontario, Canada, in 2008–2012 was conducted. Absolute and adjusted relative rates of ambulatory care visits, emergency department visits and hospitalisations for the comorbidities of interest in people with and without COPD were determined and compared. Among 7 241 591 adults, 909 948 (12.6%) had COPD. Over half of all lung cancer, a third of all lower respiratory tract infection and cardiovascular disease, a quarter of all low trauma fracture, and a fifth of all psychiatric, musculoskeletal, non-lung cancer and diabetes ambulatory care visits, emergency department visits and hospitalisations in Ontario were used by people with COPD. Individuals with COPD used about five times more health services for lung cancer, and two times more health services for lower respiratory tract infections and cardiovascular disease than people without COPD. Individuals with COPD use a disproportionate amount of health services for comorbid disease, placing significant burden on the healthcare system.
Characterization of the protease activity in the chemotactic factor inactivator.
Authors: P A Ward, J Ozols
Journal: Journal of Clinical Investigation (1976)

The chemotactic factor inactivator (CFI) isolated from human serum contains a kininase activity that causes extensive hydrolysis of bradykinin. The highly chemotactic synthetic peptide Met-Leu-Phe was completely hydrolyzed by CFI preparations. The release of the constituent amino acids from this peptide coincided with a loss of its chemotactic activity. The N-formyl, but not the amide derivative, of the leukotactic peptide Met-Leu-Phe was resistant to the action of CFI, as evidenced by chemotactic and biochemical assays. Examination of the specificity of CFI proteolysis revealed that short polypeptide substrates are degraded sequentially from the amino terminus. Larger peptides are less extensively hydrolyzed, and the patterns of hydrolysis are more complex. Inactivation of the bacterial chemotactic factors by CFI was overcome by the addition of high concentrations of peptides which were substrated for CFI. CFI preparations readily hydrolyzed the peptide Arg-Phe-Ala. The constituent amino acids were conveniently identified by thin-layer chromatography method. This procedure afforded a rapid assay for measuring CFI activity in the whole human serum as well as in fractions throughout the purification steps. Moreover, CFI also hydrolyzed L-leucyl-beta-napthylamide at rates comparable to peptides. Thus, L-leucyl-beta-napthylamide served as a useful substrate for estimating CFI activity in preparations at various stages of purification. This substrate was also useful in kinetic studies. The results from these studies indicate an aminopeptidase activity is the mechanism whereby CFI inhibits the activity of chemotactic substrates.
The Oncogene DEK Promotes Leukemic Cell Survival and Is Downregulated by both Nutlin-3 and Chlorambucil in B-Chronic Lymphocytic Leukemic Cells
Authors: Paola Secchiero, Rebecca Voltan, Maria Grazia di Iasio, Elisabetta Melloni, Mario Tiribelli, Giorgio Zauli
Journal: Clinical Cancer Research (2010)

To characterize the role of the oncogene DEK in modulating the response to either Nutlin-3, a small-molecule inhibitor of the MDM2/p53 interaction, or chlorambucil in primary B-chronic lymphocytic leukemia (B-CLL) cells.DEK mRNA and protein levels were evaluated in primary B-CLL samples (n = 21), p53(wild-type) SKW6.4, p53(mutated) BJAB lymphoblastoid cell lines, and normal CD19(+) B lymphocytes-treated Nutlin-3 or chlorambucil (10 micromol/L, each). Knocking down experiments with either p53 or DEK small interfering RNA (siRNA) were done to investigate the potential role of p53 in controlling the expression of DEK and the role of DEK in leukemic cell survival/apoptosis.Both Nutlin-3 and chlorambucil downregulated DEK in primary B-CLL samples (n = 21) and SKW6.4 but not in BJAB cells. Knocking down p53 attenuated the effect of Nutlin-3 on DEK expression, whereas knocking down DEK significantly increased both spontaneous and Nutlin-3-induced apoptosis. Conversely, counteracting DEK downmodulation by using p53 small interfering RNA reduced Nutlin-3-mediated apoptosis. On the other hand, Nutlin-3 potently induced p53 accumulation, but it did not affect DEK levels in normal CD19(+) B lymphocytes.These data show that the downregulation of DEK in response to either Nutlin-3 or chlorambucil represents an important molecular determinant in the cytotoxic response of leukemic cells, and suggest that strategies aimed to downregulate DEK might improve the therapeutic potential of these drugs.
A physiological comparison of flutter valve drainage bags and underwater seal systems for postoperative air leaks
Authors: D A Waller, J G Edwards, P B Rajesh
Journal: Thorax (1999)

<h3>BACKGROUND</h3> A study was undertaken to compare the relative physiological effects of underwater seal (UWS) versus flutter valve (FV) pleural drainage systems in the treatment of postoperative air leaks. <h3>METHOD</h3> Fourteen patients with air leaks of 1–11 days duration, following lobectomy (n = 5), bullectomy (n = 4), decortication (n = 4), and pleural biopsy (n = 1) were analysed. Intrapleural pressure (IPP) measurements were made using an in-line external strain gauge connected directly to the intercostal tube. Patients were connected simultaneously to both UWS and FV drainage systems and pressures were measured sequentially, isolating each system in turn. Maximum (IPPmax) and minimum (IPPmin) intrapleural pressures were calculated from graphic traces. The degree of lung expansion was recorded by chest radiography. <h3>RESULTS</h3> At resting tidal volume IPPmax was significantly higher with the UWS system (mean difference 0.8 mm Hg, 95% CI 0 to 1.6, p = 0.046) and IPPmin was significantly lower with the FV system (1.8 mm Hg, 95% CI 0.3 to 3.3, p = 0.023). The lung was fully expanded in 50% of patients at the time of study. The mean difference in IPPmin between systems was significantly increased when the lung was fully expanded (mean 2.8 mm Hg, 95% CI 0.1 to 5.5, p = 0.042). The mean difference in IPPmax was not affected by the degree of lung expansion (0.79, 95% CI –0.83 to 2.4, p = 0.31). <h3>CONCLUSION</h3> The results of this study suggest that, when postoperative air leak exists without a persistent pleural space, the flutter valve may provide a physiologically more effective alternative to the underwater seal drainage system.
Induction of nitric oxide synthase in human vascular smooth muscle: interactions between proinflammatory cytokines
Authors: Adrian H. Chester, Julie A.A. Borland, Lee D.K. Buttery, Jane A. Mitchell, Deirdre A. Cunningham, Sassan Hafizi, Ginette S. Hoare, David R. Springall, Julia M. Polak, Magdi H. Yacoub
Journal: Cardiovascular Research (1998)

We have attempted to demonstrate the induction of inducible nitric oxide synthase in human vascular tissue and define the capacity of different cytokines to induce this enzyme.Segments of human arteries were stimulated with lipopolysaccharide (10 micrograms/ml), interleukin-1 beta (5 U/ml), tumor necrosis factor-alpha (10 U/ml), and interferon-gamma (200 U/ml). Cytokines were either used alone or in certain combinations, as well as in the presence of L-NG-monomethyl-arginine (100 mumol/l) or cycloheximide (1 mumol/l). Induction was assessed by measurement of mRNA expression, immunocytochemical localisation of the expressed protein, nitric oxide synthase activity and levels of nitrite, a product of nitric oxide formation.PCR analysis showed the presence of mRNA for iNOS in stimulated samples which could be inhibited by cycloheximide. There was positive staining with an antibody against human iNOS in the media of stimulated vessel segments. Stimulated segments were also shown to contain Ca(2+)-independent nitric oxide synthase activity. The cytokines and lipopolysaccharide together gave a significant rise in levels of nitrite in the medium after 36 and 48 h, which was inhibited by L-NG-monomethyl-arginine and cycloheximide. Only interferon-gamma incubated alone was capable of increasing nitrite levels. This effect was enhanced by co-incubation with either interleukin-1 beta, tumor necrosis factor-alpha or lipopolysaccharide.We have shown that increased production of nitrite by human vascular tissue in response to cytokines is associated with induction of iNOS as shown at the molecular and protein levels, and further supported by the presence of increased Ca(2+)-independent nitric oxide synthase activity following cytokine stimulation.
Adenosine 5'-monophosphate in asthma: gas exchange and sputum cellular responses
Authors: H. A. Manrique, F. P. Gómez, P. A. Muñoz, A. M. Peña, J. A. Barberà, J. Roca, R. Rodríguez-Roisin
Journal: European Respiratory Journal (2008)

Adenosine 5′-monophosphate (AMP) bronchoprovocation reproduces the lung function abnormalities that occur spontaneously during acute asthma and detects peripheral airway inflammation better than direct bronchoconstrictive agents. Pulmonary gas exchange disturbances may reflect changes in small airways related to airway inflammation rather than bronchoconstriction alone. The present authors investigated whether AMP induced a greater imbalance in the ventilation/perfusion ratio than methacholine (MCh), at an equivalent degree of bronchoconstriction, with and without salbutamol pre-medication. In total, 36 asthmatics were studied in three randomised, double-blind, crossover studies: 1) before and after AMP or MCh; 2) before and 30 min after salbutamol or placebo, followed by AMP; or 3) MCh challenge. Sputum was collected before and 4 h post-challenge. Compared with MCh, AMP provoked similar pulmonary gas exchange abnormalities at an equivalent degree of intense bronchoconstriction (forced expiratory volume in one second decrease of 28–44%). While salbutamol blocked AMP- or MCh-induced bronchoconstriction, arterial oxygen tension ( P a,O 2 ) and alveolar–arterial oxygen tension difference ( P A–a,O 2 ) disturbances induced by AMP and MCh were only partially blocked ( P a,O 2 by 46 and 42%, respectively; P A–a,O 2 by 58 and 57%, respectively). Compared with MCh, AMP increased the percentage of neutrophils (mean± se increased from 28±4% to 38±4%), but this increase did not occur after salbutamol pre-treatment. Both adenosine 5′-monophosphate and methacholine induced similar peripheral airway dysfunction. The fully inhibited adenosine 5′-monophosphate-induced neutrophilia with residual hypoxaemia observed after salbutamol treatment is probably related to β 2 -agonists acting on both bronchial and pulmonary circulation.
Biological Significance of Isolated Tumor Cells and Micrometastasis in Lymph Nodes Evaluated Using a Green Fluorescent Protein–Tagged Human Gastric Cancer Cell Line
Authors: Hiroyuki Yokoyama, Hayao Nakanishi, Yasuhiro Kodera, Yuzuru Ikehara, Norifumi Ohashi, Yuichi Ito, Masahiko Koike, Michitaka Fujiwara, Masae Tatematsu, Akimasa Nakao
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The biological significance of isolated tumor cells and micrometastasis in lymph node defined by the International Union against Cancer remains essentially unknown because of the lack of appropriate animal models. In the present study, we developed a lymph node micrometastasis model featuring a human gastric cancer cell line tagged with green fluorescent protein gene (GCIY-EGFP), which allows visualization of even isolated tumor cells in the development of metastasis without histologic procedure. Using this model, we investigated the effect of surgery and chemotherapy on the growth of early-phase metastasis formation in the lymph nodes. Experimental Design: The time course of spontaneous inguinal lymph node metastasis after s.c. inoculation of GCIY-EGFP cells into nude mice was examined with fluorescence dissecting microscopy. Then, the effects of surgical removal of the primary tumor with or without anti-asialo GM1 treatment or postoperative chemotherapy on the growth of isolated tumor cells and micrometastasis in the lymph nodes were examined. Results: GCIY-EGFP cells were found to metastasize spontaneously to the inguinal lymph nodes to form isolated tumor cells, micrometastasis, and, finally, develop macroscopic metastasis at 1 to 2, 3 to 5, and 5 weeks postinjection, respectively. When the primary tumors were removed within 2 weeks of inoculation, isolated tumor cells, but not micrometastasis, in the lymph nodes regressed by 4 weeks after surgery in all the mice examined (five of five). This spontaneous regression of isolated tumor cells was completely reversed by anti-asialo GM1 treatment, which could deplete natural killer cells effectively in nude mice. Chemotherapy following resection of the primary tumor at an early stage partially eliminated the remaining micrometastasis in the lymph nodes. Conclusions: These results suggest that isolated tumor cells in the regional lymph nodes regressed by removal of the primary tumor mainly via natural killer cell–mediated antitumor activity and that micrometastasis in the lymph nodes could be effectively eliminated by the postoperative chemotherapy.
Coffee consumption and risk of colorectal cancer in a population based prospective cohort of Swedish women
Authors: P Terry
Journal: Gut (2001)

<h3>BACKGROUND</h3> The presumed protective effect of coffee consumption on colorectal cancer, which is supported by case control studies, has not been confirmed in prospective cohort studies. Cohort studies are few in number however and often suffer from a small number of cases, limited attention to confounding variables, and a low percentage of heavy coffee drinkers. <h3>METHODS</h3> We examined data from a large population based cohort of Swedish women who were free from cancer at the start of follow up, with a wide range of coffee consumption, information on many potentially confounding variables, and a larger number of cases than any previous cohort study of coffee consumption and colorectal cancer. <h3>RESULTS</h3> During an average of 9.6 years of follow up of 61 463 women aged 40–74 years, we observed 460 incident cases of colorectal cancer (291 with colon cancer, 159 with rectal cancer, 10 with cancer at both sites). We found no association between coffee consumption and colorectal cancer risk. The risk ratio for drinking four or more cups per day compared with none was 1.04 (95% confidence interval 0.63—1.69; p for trend 0.84). The findings were similar for cancers of the distal and proximal colon and rectum. <h3>CONCLUSIONS</h3> The recently published affirmative conclusions regarding the protective effect of coffee consumption may be premature. For patients seeking advice about coffee consumption, the evidence suggests that moderate or even high consumption will probably not influence the risk of colorectal cancer.
504 HBV quasispecies selected during lamivudine treatment may contribute to adefovir dipivoxil resistance
Authors: E. Moriconil, D. Flichman, P. Ciccorossi, B. Coco, R. Sacco, E. Oliveri, E. Colombatto, E. Bonino, M.R. Brunetto
Journal: Journal of Hepatology (2006)
Skin biopsy rates and incidence of melanoma: population based ecological study
Authors: H Gilbert Welch, Steven Woloshin, Lisa M Schwartz
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To describe changes in skin biopsy rates and to determine their relation with changes in the incidence of melanoma. <b>Design</b> Population based ecological study. <b>Setting</b> Nine geographical areas of the United States. <b>Participants</b> Participants of the Surveillance Epidemiology and End Results (SEER) programme aged 65 and older. <b>Main outcome measures</b> For the period 1986 to 2001, annual skin biopsy rates for each surveillance area from Medicare claims and incidence rates for melanoma for the same population. <b>Results</b> Between 1986 and 2001 the average biopsy rate across the nine participating areas increased 2.5-fold among people aged 65 and older (2847 to 7222 per 100 000 population). Over the same period the average incidence of melanoma increased 2.4-fold (45 to 108 per 100 000 population). Assuming that the occurrence of true disease was constant, the extra number of melanoma cases that were diagnosed after carrying out 1000 additional biopsies was 12.6 (95% confidence interval 11.2 to 14.0). After controlling for a potential increase in the true occurrence of disease, 1000 additional biopsies were still associated with 6.9 (3.1 to 10.8) extra melanoma cases diagnosed. Stage specific analyses suggested that 1000 biopsies were associated with 4.4 (2.1 to 6.8) extra cases of in situ melanoma diagnosed and 2.3 (0.0 to 4.6) extra cases of local melanoma, but not with the incidence of advanced melanoma. Mortality from melanoma changed little during the period. <b>Conclusion</b> The incidence of melanoma is associated with biopsy rates. That the extra cases diagnosed were confined to early stage cancer while mortality remained stable suggests overdiagnosis—the increased incidence being largely the result of increased diagnostic scrutiny and not an increase in the incidence of disease.
Mechanically induced action potential changes and arrhythmia in isolated and in situ canine hearts
Authors: M. R FRANZ, D. BURKHOFF, D. T YUE, K. SAGAWA
Journal: Cardiovascular Research (1989)

Stretch of excised myocardial tissue causes electrophysiological and potentially arrhythmogenic changes in transmembrane action potentials but corresponding data of the intact mammalian heart are lacking. The effects of increases in ventricular volume and pressure on epicardial monophasic action potentials were therefore investigated in isolated, cross circulated and in situ canine hearts. In seven isolated hearts, increases in ventricular volume and pressure resulted in (1) a linearly related decrease in action potential amplitude (r = 0.988; slope = 0.41% amplitude·ml−1; volume intercept = 17.6 ml), mainly due to a decrease in maximum diastolic potential; (2) a decrease in action potential plateau duration (at 20% repolarisation) by 19 (SD 8)%; and (3) appearance of early afterdepolarisations, reaching up to 18% of total action potential amplitude. Afterdepolarisations occurred only when ventricular outflow was obstructed at end diastole but not at end systole. In eight in situ hearts, increase in left intraventricular pressure produced by transient occlusions of the ascending aorta was also accompanied by decrease in maximum diastolic potential and action potential plateau duration, and by appearance of early afterdepolarisations. In both isolated and in situ intact ventricles, the loading induced electrophysiological changes were associated with occurrence of ectopic ventricular beats. These data show that mechanical overload produces significant electrophysiological changes in the intact canine ventricle which may lead to arrhythmia.
Splenic volume can be a novel predictive parameter for the prognosis of chronic lymphocytic leukemia?
Authors: M.-K. Song, J.-S. Chung, H.-S. Lee, S.-H. Kim, None Suk-Kim, E.-Y. Yun, Y.-M. Seol, H.-J. Shin, Y.-J. Choi, G.-J. Cho
Journal: Annals of Oncology (2010)
Validation of Ottawa ankle rules protocol in Greek athletes: study in the emergency departments of a district general hospital and a sports injuries clinic
Authors: E Papacostas, N Malliaropoulos, A Papadopoulos, C Liouliakis
Journal: British Journal of Sports Medicine (2001)

To validate the Ottawa ankle rules protocol for predicting ankle and midfoot fractures in Greek athletes.A prospective survey in the emergency departments of a district general hospital and a sports injury clinic in Greece over nine months. A clinical evaluation was made of 122 patients with acute ankle and/or midfoot injury, and then radiographs were taken.Nine ankle and eight midfoot fractures were detected. The sensitivity of the Ottawa ankle rules protocol in predicting fractures in both the malleolar and midfoot zones was 100%. The negative predictive value for each of these areas was also 1.0. Specificity was estimated to be 0.3 for ankle fractures and 0.4 for midfoot fractures. Positive predictive values were 0.16 and 0.28 respectively. A possible reduction of up to 28.7% was found in the need for radiography.Use of the Ottawa ankle rules protocol in evaluating injured Greek athletes resulted in 100% sensitivity when performed by orthopaedic residents or sports medicine doctors, and had the potential to reduce the use of radiography.