tbuckley/cabot-search huggingface dataset:
The impact of comorbidities on the short-term serious health outcomes in hospitalized COPD patients due to exacerbation
Authors: Sibel Atis Nayci, Eylem Özgür, Cengiz Özge, Yasin Duman, Esin Tastekin, Ahmet Ilvan
Journal: European Respiratory Journal (2013)

The comorbidities are frequent in hospitalized COPD patients but little is known about their association with the serious health outcomes. We aimed to assess the relationship between comorbidities and the short-term serious health outcomes in hospitalized COPD patients due to exacerbation.

We analysed data of 72 COPD patients who hospitalized due to exacerbation. We evaluated comorbidities, need of ICU, mortality during hospitalization, and re-hospitalization and mortality within 3 months after discharge. Risk factors (smoking, FEV1, MRC, exacerbation frequecy and comorbidities) were investigated for these outcomes.

The frequent comorbidities were: Hypertension (48.6%), ischemic heart disease (36.1%), diabetes (27.8%), heart failure (26.4%), cachexia (20.8%), obesity (19.4%), anemia (19.4%), dyslipidemia (18.1%), kidney disease (13.9%), depression (12.5%). Eight (11.1%) patients died during hospitalization, and 14 (21.9%) within 3 months. 10 (15.6%) patients had re-hospitalization, 21 (29.2%) required ICU. MRC (p=0.004), cachexia(p=0.002), anemia (p=0.021) were independent risk factors for mortality during hospitalization. MRC (p=0.001), depression (p=0.048), dyslipidemia (p=0.015), obesity (0.046) were independent risk factors for the need of ICU. Kidney disease (p=0.013), diabetes (p=0.050) were independent risk factors for mortality within 3 months. Depression (p=0.026) was the independent risk factor for re-hospitalization.

This study showed that dyspnea degree and comorbidities are related to the short-term serious health outcomes in COPD. Detailed evaluation and treatment of these associated comorbidities may improve the shortime-prognosis of this patients.
A High-Carbohydrate, High-Fiber Meal Improves Endothelial Function in Adults With the Metabolic Syndrome
Authors: David W. Brock, Christopher K. Davis, Brian A. Irving, Jessica Rodriguez, Eugene J. Barrett, Arthur Weltman, Ann Gill Taylor, Glenn A. Gaesser
Journal: Diabetes Care (2006)

Brachial artery flow-mediated dilation (FMD) using high-resolution ultrasound is a well-accepted, noninvasive bioassay for in vivo endothelium-generated nitric oxide (NO) in humans (1). Impaired NO generation characterizes the endothelial phenotype prone to the development of atherosclerosis and is linked to acute cardiovascular events. In several studies (2,3), endothelial dysfunction is an independent predictor of future cardiovascular morbidity and mortality. The postprandial state may be critical in the development of atherosclerosis (4). A single high-fat meal can induce endothelial dysfunction, whereas low-fat meals generally neither improve nor worsen FMD (5–8). The lack of a reported effect of low-fat meals on FMD may be attributable in part to insufficient dietary fiber in the meal. In particular, increased cereal fiber consumption is associated with reduced cardiovascular disease incidence and mortality (9–11) and lower prevalence of the metabolic syndrome (12) and may reduce systemic inflammation (13). We examined whether a high-carbohydrate meal, rich in cereal fiber, would improve brachial artery FMD in adults with the metabolic syndrome. For comparison, we also examined the impact of a low-carbohydrate, low-fiber meal.

Twelve (9 women and 3 men: 44.7 ± 7.9 years of age, 98.9 ± 16.6 kg, 1.70 ± 0.07 m) nonsmoking, nondiabetic adults who met the International Diabetes Federation criteria for the metabolic syndrome participated in the study (14). Subjects were not taking medications to control blood lipids, blood …
Role of symptoms and lung function in determining asthma control in smokers with asthma
Authors: R. Chaudhuri, C. McSharry, A. McCoard, E. Livingston, E. Hothersall, M. Spears, J. Lafferty, N. C. Thomson
Journal: Allergy (2007)

Background: Cigarette smoking in asthma increases the severity and accelerates the decline in lung function. The relative role of symptoms and lung function in determining asthma control in smokers with asthma is not known. Aim of the study: The aim of this study was to compare asthma control in smokers vs never‐smokers with asthma, using the validated Juniper asthma control questionnaire (ACQ), and assess if any difference was because of a particular symptom or the forced expiratory volume in one second (FEV 1 ) value. Methods: This was a cross‐sectional study of 134 asthmatics (74 never‐smokers and 60 smokers) with ≥15% reversibility in FEV 1 after salbutamol. All subjects completed the ACQ, recording FEV 1 and asthma symptoms (night awakening, morning symptoms, dyspnoea, wheeze, activity limitation and use of reliever inhaler). Results: Compared with the never‐smokers, smokers with asthma had significantly worse median (IQR) total asthma control score [1.6 (1.1–2.3) vs 2.8 (1.7–3.4); ( P &lt; 0.0001)] and in each of the six individual symptom question scores ( P &lt; 0.001), but no difference in FEV 1 levels ( P = 0.908). Conclusion: Asthma control is significantly worse in asthmatics who smoke compared with never‐smokers, with all symptoms related to asthma control uniformly worse in smokers, independent of FEV 1 .
Inhalant Corticosteroids Inhibit Hyperosmolarity-induced, and Cooling and Rewarming–induced Interleukin-8 and RANTES Production by Human Bronchial Epithelial Cells
Authors: SHU HASHIMOTO, YASUHIRO GON, KEN MATSUMOTO, IKUKO TAKESHITA, SHUICHIRO MARUOKA, TAKASHI HORIE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Inhaled corticosteroids are widely used for the treatment of bronchial asthma, and a long-term treatment with inhaled corticosteroids is effective in preventing exercise-induced bronchoconstriction (EIB). We have previously shown that hyperosmolarity, and cooling and rewarming induced interleukin-8 (IL-8) expression in human bronchial epithelial cells (BEC). However, the effect of inhalant corticosteroids on hyperosmolarity-induced, and cooling and rewarming–induced IL-8 and RANTES production has not been determined. To clarify these issues, we examined the effect of inhalant corticosteroids, beclomethasone dipropionate (BDP), and budesonide (BUD) on hyperosmolarity-induced, and cooling and rewarming–induced IL-8 and RANTES production. The results showed that BDP and BUD inhibited hyperosmolarity-induced, and cooling and rewarming–induced IL-8 and RANTES production. Because our previous studies have shown that p38 mitogen-activated protein (MAP) kinase and c-Jun-NH2-terminal kinase (JNK) regulate hyperosmolarity-induced, and cooling and rewarming–induced IL-8 and RANTES production, we examined the effect of BDP and BUD on p38 MAP kinase and JNK activation. The results showed that BDP and BUD did not inhibit hyperosmolarity-induced and cooling-induced p38 MAP kinase and JNK activation. These results indicated that inhalant corticosteroids inhibited hyperosmolarity-, and cooling and rewarming–induced IL-8 and RANTES production; however, the mechanism of inhaled corticosteroid–mediated inhibition of hyperosmolarity-induced, and cooling and rewarming– induced cytokine production remains to be clarified.
The Four Apostles of Surgery: An Historical Sketch
Authors: G. H. B. Macleod
Journal: BMJ (1877)

GENTLEMEN,-My first duty, on taking this chair, is to acknowledge the honour you have done me in selecting me as your President.I need not say how much I appreciate this mark of your confidence, especially as this is but the second occasion on which you have exercised your right of choice.I regard your kindness the Wore highly, as Isuc- ceed a man so respected and honoured as Professor Alen Thomson.Having, first as a student and latterly as a colleague, come much into contact
Chlorogenic acid inhibits Bcr-Abl tyrosine kinase and triggers p38 mitogen-activated protein kinase–dependent apoptosis in chronic myelogenous leukemic cells
Authors: Gautam Bandyopadhyay, Tanusree Biswas, Keshab C. Roy, Swapan Mandal, Chhabinath Mandal, Bikas C. Pal, Samir Bhattacharya, Srabanti Rakshit, Dilip K. Bhattacharya, Utpal Chaudhuri, Aditya Konar, Santu Bandyopadhyay
Journal: Blood (2004)
Cardiac Troponin T and C-Reactive Protein for Predicting Prognosis, Coronary Atherosclerosis, and Cardiomyopathy in Patients Undergoing Long-term Hemodialysis
Authors: Christopher DeFilippi, Steven Wasserman, Salvatore Rosanio, Eric Tiblier, Heidi Sperger, Monica Tocchi, Robert Christenson, Barry Uretsky, Mathew Smiley, Judith Gold, Henry Muniz, John Badalamenti, Charles Herzog, William L Henrich
Journal: JAMA (2003)

Cardiac troponin T (cTnT) and C-reactive protein (CRP) are prognostic markers in acute coronary syndromes. However, for patients with end-stage renal disease (ESRD) the ability of combinations of these markers to predict outcomes, and their association with cardiac pathology, are unclear.To investigate the association between levels of cTnT and CRP and long-term risk of cardiac pathology and death in patients with ESRD.A prospective cohort study initiated February through June 1998 and enrolling 224 patients with ESRD from 5 hemodialysis centers in the Houston-Galveston region of Texas. Levels of cTnT and CRP were analyzed at study entry in patients without ischemic symptoms.All-cause mortality during a mean follow-up of 827 (range, 29-1327) days. Secondary outcomes in predefined substudies were coronary artery disease (CAD), decreased (< or =40%) left ventricular ejection fraction (LVEF), and presence of left ventricular hypertrophy (LVH).One hundred seventeen (52%) patients died during follow-up. For levels of cTnT and CRP, progressively higher levels predicted increased risk of death compared with the lowest quartile (for cTnT quartile 2: unadjusted hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.2-4.1; quartile 3: HR, 2.7; 95% CI, 1.5-4.9; quartile 4: HR, 3.0; 95% CI, 1.6-5.3. For CRP quartile 2: HR, 0.9; 95% CI, 0.5-1.6; quartile 3: HR, 1.8; 95% CI, 1.1-3.1; quartile 4: HR, 1.8; 95% CI, 1.1-3.2). Both cTnT and CRP remained independent predictors of death after adjusting for a number of potential confounders. The combination of cTnT and CRP results provided prognostic information when patients were divided into groups at or above and below the biomarker medians (high cTnT/high CRP levels vs low cTnT/low CRP levels for risk of death: HR, 2.5; 95% CI, 1.5-4.0). Elevated levels of cTnT, but not CRP, were strongly associated with diffuse CAD (n = 67; 0%, 25%, 50%, and 62% prevalence of multivessel CAD across progressive cTnT quartiles, P<.001). An LVEF of 40% or less was identified in 4 (9%), 3 (8%), 10 (27%), and 7 (19%) of patients across cTnT quartiles (P =.07). No trend for cTnT levels was found among patients with LVH (P =.45); similarly, no trend for CRP was found among patients with LVH (P =.65) or an LVEF of 40% or less (P =.75).Among stable patients with ESRD, increasing levels of cTnT and CRP are associated with increased risk of death. Furthermore, higher levels of cTnT may identify patients with severe angiographic coronary disease.
Sonic Hedgehog Is a Novel Tubule-Derived Growth Factor for Interstitial Fibroblasts after Kidney Injury
Authors: Dong Zhou, Yingjian Li, Lili Zhou, Roderick J. Tan, Liangxiang Xiao, Min Liang, Fan Fan Hou, Youhua Liu
Journal: Journal of the American Society of Nephrology (2014)

Tubular epithelium constitutes the majority of the renal parenchyma and is the primary target of various kidney injuries. However, how the injured tubules drive interstitial fibroblast activation and proliferation remains poorly understood. Here, we investigated the role of sonic hedgehog (Shh), a secreted extracellular signaling protein, in fibroblast proliferation. Shh was induced in renal tubular epithelia in animal models of CKD induced by ischemia/reperfusion injury (IRI), adriamycin, or renal mass ablation, and in renal tubules of kidney biopsy specimens from CKD patients with different etiologies. Using Gli1-CreER(T2) reporter mice, we identified interstitial fibroblasts as the principal targets of renal Shh signaling in vivo. In vitro, incubation with Shh promoted normal rat kidney fibroblast proliferation, which was assessed by cell counting, MTT assay, and BrdU incorporation assay, and stimulated the induction of numerous proliferation-related genes. However, Shh had no effect on the proliferation of renal tubular epithelial cells. In vivo, overexpression of Shh promoted fibroblast expansion and aggravated kidney fibrotic lesions after IRI. Correspondingly, blockade of Shh signaling by cyclopamine, a small molecule inhibitor of Smoothened, inhibited fibroblast proliferation, reduced myofibroblast accumulation, and attenuated renal fibrosis. These studies identify Shh as a novel, specific, and potent tubule-derived growth factor that promotes interstitial fibroblast proliferation and activation. Our data also suggest that blockade of Shh signaling is a plausible strategy for therapeutic intervention of renal fibrosis.
Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevents acute pancreatitis by protecting production of ATP
Authors: Rajarshi Mukherjee, Olga A Mareninova, Irina V Odinokova, Wei Huang, John Murphy, Michael Chvanov, Muhammad A Javed, Li Wen, David M Booth, Matthew C Cane, Muhammad Awais, Bruno Gavillet, Rebecca M Pruss, Sophie Schaller, Jeffery D Molkentin, Alexei V Tepikin, Ole H Petersen, Stephen J Pandol, Ilya Gukovsky, David N Criddle, Anna S Gukovskaya, Robert Sutton
Journal: Gut (2015)

<h3>Objective</h3> Acute pancreatitis is caused by toxins that induce acinar cell calcium overload, zymogen activation, cytokine release and cell death, yet is without specific drug therapy. Mitochondrial dysfunction has been implicated but the mechanism not established. <h3>Design</h3> We investigated the mechanism of induction and consequences of the mitochondrial permeability transition pore (MPTP) in the pancreas using cell biological methods including confocal microscopy, patch clamp technology and multiple clinically representative disease models. Effects of genetic and pharmacological inhibition of the MPTP were examined in isolated murine and human pancreatic acinar cells, and in hyperstimulation, bile acid, alcoholic and choline-deficient, ethionine-supplemented acute pancreatitis. <h3>Results</h3> MPTP opening was mediated by toxin-induced inositol trisphosphate and ryanodine receptor calcium channel release, and resulted in diminished ATP production, leading to impaired calcium clearance, defective autophagy, zymogen activation, cytokine production, phosphoglycerate mutase 5 activation and necrosis, which was prevented by intracellular ATP supplementation. When MPTP opening was inhibited genetically or pharmacologically, all biochemical, immunological and histopathological responses of acute pancreatitis in all four models were reduced or abolished. <h3>Conclusions</h3> This work demonstrates the mechanism and consequences of MPTP opening to be fundamental to multiple forms of acute pancreatitis and validates the MPTP as a drug target for this disease.
Therapeutic Implications of Leukemia Stem Cell Development
Authors: Matthew C. Stubbs, Scott A. Armstrong
Journal: Clinical Cancer Research (2007)

Abstract Acute myelogenous leukemias, and perhaps many other cancers, are maintained by a population of cancer stem cells that can regenerate themselves as well as give rise to more differentiated and less proliferative cells that constitute the bulk of the disease. Recent discoveries have shed light on both the nature of leukemia stem cells (LSC) and their cells of origin. Here, we review which hematopoietic cells could give rise to LSC, and the phenotype of fully developed LSC. The perturbed developmental pathways and cellular context of LSC development have implications for the development of new therapeutic approaches.
Profession of Medicine: A Study of the Sociology of Applied Knowledge
Authors: Amas B. Ford
Journal: JAMA (1970)

Buried in the pedantic pages of this book is a pointed challenge to medicine. Simply stated, Freidson's view is that the medical profession has become too autonomous and too powerful for the good of society, and that it must therefore be regulated. Like the prominent medical sociologist he is, the author develops his argument through an exhaustive theoretical analysis. He begins with the formal organization of the profession and proceeds to the ways in which the performance of its work is organized and regulated. He denies that the knowledge required for clinical practice is so esoteric that it cannot be questioned by lay persons. The "clinical mentality" he finds to be characterized by action orientation and pragmatism. Physicians, he concedes, do have a service orientation as well, but he believes it to be not prominent and not a sufficient basis for claims to professional autonomy. Physicians expect to be allowed
Protective Role for Interferon-β in Coxsackievirus B3 Infection
Authors: Raj Deonarain, Dante Cerullo, Koichi Fuse, Peter P. Liu, Eleanor N. Fish
Journal: Circulation (2004)

Coxsackievirus-induced myocarditis can be a serious cause of heart failure. In the absence of a specific antiviral therapy, modulating the host immune response may be protective. Interferons (IFNs)-alpha and -beta perform a fundamental role in innate and adaptive antiviral responses, thereby presenting as candidate therapeutics for coxsackievirus infections.To examine the contribution of IFN-beta in protection from coxsackievirus B3 (CVB3) infection, mice lacking the IFN-beta gene were infected with 10(3) plaque-forming units of CVB3. In contrast to wild-type mice that exhibit an intact IFN-beta response, we observed increased susceptibility to infection (70% mortality), a downregulation of IFN-stimulated gene targets (2'-5' oligoadenylate synthetase, serine/threonine protein kinase, the GTPase Mx), and cardiomyocyte breakdown and disruption in the IFN-beta-/- mice.Viewed together, these results clearly demonstrate that IFN-beta is important in mediating protection against CVB3-induced myocarditis.
Outdoor Formaldehyde and NO <sub>2</sub> Exposures and Markers of Genotoxicity in Children Living Near Chipboard Industries
Authors: Alessandro Marcon, Maria Enrica Fracasso, Pierpaolo Marchetti, Denise Doria, Paolo Girardi, Linda Guarda, Giancarlo Pesce, Vanda Pironi, Paolo Ricci, Roberto de Marco
Journal: Environmental Health Perspectives (2014)

Industrial air pollution is a public health hazard. Previous evidence documented increased respiratory symptoms and hospitalizations in children who live near the factories in the largest chipboard manufacturing district in Italy (Viadana).We evaluated the association of outdoor exposure to formaldehyde and nitrogen dioxide (NO2) with markers of early genotoxic damage in oral mucosa cells of randomly selected children (6-12 years of age) living in Viadana.In 2010-2011, DNA strand breaks and nuclear abnormalities were evaluated in exfoliated buccal cells by the comet and micronucleus assays, respectively, and formaldehyde and NO2 were monitored by passive sampling. Annual exposure estimates to pollutants were assigned to children's houses by spatial interpolation.Of 656 children, 413 (63%) participated. Children living near (< 2 km) the chipboard industries had the highest average exposure to formaldehyde and NO2 (p < 0.001). A 1-SD increase in formaldehyde (0.20 μg/m(3)) was associated with a 0.13% (95% CI: 0.03, 0.22%) higher comet tail intensity, a 0.007 (95% CI: 0.001, 0.012) higher tail moment, and a 12% relative increase [relative risk (RR) = 1.12; 95% CI: 1.02, 1.23] in nuclear buds. A 1-SD NO2 increase (2.13 μg/m(3)) was associated with a 0.13% (95% CI: 0.07, 0.19%) increase in binucleated cells and a 16% relative increase (RR = 1.16; 95% CI: 1.06, 1.26) in nuclear buds.Exposure to pollutants was associated with markers of genotoxicity in exfoliated buccal cells of children living in a region with chipboard industries. These findings, combined with previously reported associations between chipboard industrial activities and respiratory outcomes in children, add to concerns about potential adverse effects of industry-related exposures in the Viadana district.
Influence of Pulmonary Bacteriology and Histology on the Yield of Diagnostic Procedures in Ventilator-Acquired Pneumonia
Authors: DELPHINE WERMERT, CHARLES-HUGO MARQUETTE, MARIE-CHRISTINE COPIN, FRÉDÉRIC WALLET, ANNE FRATICELLI, PHILIPPE RAMON, ANDRÉ-BERNARD TONNEL
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

We investigated the influence of pulmonary bacteriology and histology on the yield of diagnostic procedures in a clinically relevant model of ventilator-acquired pneumonia (VAP). Twenty-seven piglets entered a 4-d protocol of ventilatory support under general anesthesia. Endotracheal aspirates (EA), protected specimen brush (PSB), and bronchoalveolar lavage (BAL) were obtained on Day 4. PSB and BAL were performed under bronchoscopic guidance in dependent and nondependent lung segments. Immediately thereafter sternotomy allowed bilateral lung biopsies including the segments studied by bronchoscopic techniques. All respiratory specimens were then processed for microscopic examination and quantitative cultures (QC). In this model where many of the confounding factors often present in human studies were absent, we found that (1) although the local bacterial burden tended to correlate with the presence and the severity of histologic lesions, no definite bacteriologic cutoff could differentiate the histologic presence or absence of pneumonia; (2) histologic lesions of pneumonia and parenchymal bacterial burden were unevenly distributed through the lungs; (3) this heterogeneity in bacterial distribution also held true for single bacterial species; (4) using discriminative values of ⩾ 103 cfu/ml, ⩾ 104 cfu/ml, and ⩾ 105 cfu/ml to define positive PSB, BAL, and EA cultures, respectively, these techniques identified the histologic presence of pneumonia with a sensitivity of 69%, 78%, and 100%, respectively; (5) the specificity of these techniques in recognizing VAP was less than 50%; (6 ) with these discriminative values, less than 50% of PSB and BAL specimens correctly identified the causative organisms, whereas 94% of EA specimens correctly established the microbiologic diagnosis of pneumonia. We believe that the peculiar histologic and bacteriologic features of VAP may account for the difficulties of PSB and BAL, which combine QC with the use of discriminative thresholds, to reliably recognize pneumonia and to identify the causative organisms. For clinical practice, no technique confidently helps in recognizing pneumonia in mechanically ventilated patients. With regard to bacterial diagnosis, use of quantitative cultures of EA seems to be the best technique to identify the causative organisms in patients suffering VAP.
The interaction of anticancer therapies with tumor-associated macrophages
Authors: Alberto Mantovani, Paola Allavena
Journal: The Journal of Experimental Medicine (2015)

Macrophages are essential components of the inflammatory microenvironment of tumors. Conventional treatment modalities (chemotherapy and radiotherapy), targeted drugs, antiangiogenic agents, and immunotherapy, including checkpoint blockade, all profoundly influence or depend on the function of tumor-associated macrophages (TAMs). Chemotherapy and radiotherapy can have dual influences on TAMs in that a misdirected macrophage-orchestrated tissue repair response can result in chemoresistance, but in other circumstances, TAMs are essential for effective therapy. A better understanding of the interaction of anticancer therapies with innate immunity, and TAMs in particular, may pave the way to better patient selection and innovative combinations of conventional approaches with immunotherapy.