tbuckley/cabot-search huggingface dataset:
Inhaled colistin following lung transplantation in colonised cystic fibrosis patients: Table 1–
Authors: Hendrik Suhling, Jessica Rademacher, Mark Greer, Axel Haverich, Gregor Warnecke, Jens Gottlieb, Tobias Welte
Journal: European Respiratory Journal (2013)

Inhaled colistin following lung transplantation in colonised cystic fibrosis patientsTo the Editor:Respiratory tract infections due to viral, bacterial or even fungal pathogens are common after lung transplantation [1].Previous studies demonstrated increased hospitalisation rates and a greater risk of chronic lung allograft dysfunction in colonised patients with cystic fibrosis (CF) [2].Positive effects of inhaled antibiotics have been demonstrated for pneumonia in non-transplant patients with improvements of lung function, hospitalisation rates and need for i.v.antibiotics [3,4].Inhaled colistin is known to provide high drug concentrations in sputum while low systemic concentrations occur and treatment is well tolerated [5].Here, the impact of inhaled colistin, both in reducing bacterial load in previously colonised patients and as a preventive therapy in non-colonised CF patients, after lung transplantation, was studied in a retrospective single-centre study (Hanover Medical School, Hanover, Germany).CF patients who underwent lung transplantation between January 1, 2005 and May 1, 2011 were included and follow-up continued until June 6, 2011.Perioperative antibiotics were continued for 2 weeks after lung transplantation, consisting of combination therapy based on previous microbiological findings.A routine surveillance programme at 1, 3, 6, 9 and 12 months after transplantation included pulmonary function testing, blood gas analysis and bronchoscopy with bronchoalveolar lavage (BAL).Quantitative microbial status was assessed by microbial investigation of BAL, as previously described [6].According to the presence of bacteria in the first BAL following lung transplantation, patients were categorised as 1) patients with colonisation or 2) patients without colonisation.Within these two groups, patients were subclassified depending on their treatment with inhaled colistin, as there was no standardised protocol for beginning colistin inhalation.The inhalation of colistin (1 million IU twice daily) was started immediately after transplantation (PARI BOY; PARI GmbH, Starnberg, Germany) and only patients with at least 3 months continuous colistin use after transplantation were allocated to the colistin-treated groups.All potential pathogens were included in analysis and the presence of o1 bacterial colony after 48 h of culturing was considered significant.Colonisation was defined as repeated detection of the same pathogen in two consecutive BALs.Timing of eradication was defined as the first of three consecutive negative cultures.Statistical analysis was performed using SPSS Version 18 (SPSS Inc., Chicago, IL, USA).All reported pvalues are two-sided and p-values ,0.05 were considered statistically significant.Chi-squared test and t-test were performed.
Life-threatening ventricular arrhythmias due to transient or correctable causes: high risk for death in follow-up
Authors: D.George Wyse, Peter L Friedman, Michael A Brodsky, Karen J Beckman, Mark D Carlson, Anne B Curtis, Alfred P Hallstrom, Merritt H Raitt, Bruce L Wilkoff, H.Leon Greene
Journal: Journal of the American College of Cardiology (2001)
I<scp>N</scp> V<scp>IVO</scp> K<scp>INETICS OF</scp> F<scp>OLATE</scp> M<scp>ETABOLISM</scp>
Authors: Jesse F. Gregory III, Eoin P. Quinlivan
Journal: Annual Review of Nutrition (2002)

▪ Abstract Investigation of the in vivo kinetics of folate metabolism provides information that contributes to a better understanding of the manner in which this vitamin is processed in vivo. Kinetic studies can yield insight into the requirements for folate, especially with respect to factors that may lead to increased requirements. This review considers the strengths and weaknesses of various approaches to the study of folate kinetics and resulting data, followed by a summary and interpretation of existing data.
Neutrophil proteases alter the interleukin-22-receptor-dependent lung antimicrobial defence
Authors: Antoine Guillon, Youenn Jouan, Deborah Brea, Fabien Gueugnon, Emilie Dalloneau, Thomas Baranek, Clémence Henry, Eric Morello, Jean-Christophe Renauld, Muriel Pichavant, Philippe Gosset, Yves Courty, Patrice Diot, Mustapha Si-Tahar
Journal: European Respiratory Journal (2015)

Chronic obstructive pulmonary disease (COPD) is punctuated by episodes of infection-driven acute exacerbations. Despite the life-threatening nature of these exacerbations, the underlying mechanisms remain unclear, although a high number of neutrophils in the lungs of COPD patients is known to correlate with poor prognosis. Interleukin (IL)-22 is a cytokine that plays a pivotal role in lung antimicrobial defence and tissue protection. We hypothesised that neutrophils secrete proteases that may have adverse effects in COPD, by altering the IL-22 receptor (IL-22R)-dependent signalling. Using in vitro and in vivo approaches as well as reverse transcriptase quantitative PCR, flow cytometry and/or Western blotting techniques, we first showed that pathogens such as the influenza virus promote IL-22R expression in human bronchial epithelial cells, whereas Pseudomonas aeruginosa , bacterial lipopolysaccharide or cigarette smoke do not. Most importantly, neutrophil proteases cleave IL-22R and impair IL-22-dependent immune signalling and expression of antimicrobial effectors such as β-defensin-2. This proteolysis resulted in the release of a soluble fragment of IL-22R, which was detectable both in cellular and animal models as well as in sputa from COPD patients with acute exacerbations. Hence, our study reveals an unsuspected regulation by the proteolytic action of neutrophil enzymes of IL-22-dependent lung host response. This process probably enhances pathogen replication, and ultimately COPD exacerbations.
Peginterferon Pharmacokinetics in African American and Caucasian American Patients With Hepatitis C Virus Genotype 1 Infection
Authors: Charles D. Howell, Thomas C. Dowling, Marika Paul, Abdus S. Wahed, Norah A. Terrault, Milton Taylor, Lennox Jeffers, Jay H. Hoofnagle
Journal: Clinical Gastroenterology and Hepatology (2008)
Quadriceps muscle oxygenation parameters during exercise in ILD patients
Authors: Shinichi Arizono, Hiroyuki Taniguchi, Yasuhiro Kondoh, Tomoki Kimura, Kensuke Kataoka, Tomoya Ogawa, Fumiko Watanabe, Jun Hirasawa, Takuro Furukawa, Kazuyuki Tabira
Journal: European Respiratory Journal (2014)

Background:  Poor exercise capacity was related the impaired quadriceps muscles function in patients with interstitial lung diseases (ILD). In normal subjects, tissue oxygen saturation (StO 2 ) in Quadriceps muscle related exercise capacity. ILD patients have severe hypoxia during exercise. We hypothesized that the SpO 2  - StO 2  which was considered exercise induced hypoxia would be usefulmuscle oxygenation parameter than the StO 2 . The purpose of the present study was to compare the SpO 2  - StO 2  and the StO 2  in relation to exercise capacity, pulmonary functional, dyspnea and health status in ILD patients.   Methods : Forty ILD patients (%VC: 88.8±19.0%) were measured cardiopulmonary exercise test (CPET), pulmonary functional test (%VC, %DLco), dyspnea (Baseline dyspnea index: BDI), health status (St. George9s Respiratory Questionnaire: SGRQ), muscle strength tests. During CPET, we continuously monitored SpO 2 , and measured StO 2  in Quadriceps muscle with continuous-wave near-infrared spectroscopy. We calculated Pearson correlation coefficients to examine the relationships between the StO 2 , the SpO 2  - StO 2  and measurements.   Results:  At the end of CPET, the StO 2  was 52.9%, the SpO 2  - StO 2  was 35.5%. StO 2  was significantly correlated only with %DLco (p 2  - StO 2  was significantly correlated with peakVO 2 , %VC, %DLco, BDI, SGRQ, and SpO 2 (p   Conclusion:  In ILD patients, our study showed that the SpO 2  - StO 2  may be useful muscle oxygenation parameter than the StO 2 .
Stroke After Thrombolysis
Authors: Joel M. Gore, Christopher B. Granger, Maarten L. Simoons, Michael A. Sloan, W. Douglas Weaver, Harvey D. White, Gabriel I. Barbash, Frans Van de Werf, Philip E. Aylward, Eric J. Topol, Robert M. Califf
Journal: Circulation (1995)

Background Stroke is the most feared complication of thrombolysis for acute myocardial infarction because of the resulting mortality and disability. We analyzed the incidence, timing, and outcomes of stroke in an international trial. Methods and Results Patients were randomly assigned to one of four thrombolytic strategies. Neurological events were confirmed clinically and anatomically and were adjudicated by a blinded committee. Stroke survivors, categorized by residual deficit and disability, assessed their quality of life with a time trade-off technique. Multivariable regression identified patient characteristics associated with intracranial hemorrhage. Overall, 1.4% of the patients had a stroke (93% anatomic documentation). The risk ranged from 1.19% with streptokinase/subcutaneous heparin therapy to 1.64% with combination thrombolytic therapy ( P =.007). Primary intracranial hemorrhage rates ranged from 0.46% with streptokinase/subcutaneous heparin to 0.88% with combination therapy ( P &lt;.001). Of all strokes, 41% were fatal, 31% were disabling, and 24% were nondisabling, with no significant treatment-related differences. Stroke subtype affected prognosis: 60% of patients with primary intracranial hemorrhage died and 25% were disabled versus 17% dead and 40% disabled with nonhemorrhagic infarctions. Patients with moderate or severe residual deficits showed significantly decreased quality of life. Advanced age, lower weight, prior cerebrovascular disease or hypertension, systolic and diastolic blood pressures, randomization to tissue plasminogen activator, and an interaction between age and hypertension were significant predictors of intracranial hemorrhage. Conclusions Stroke remains a rare but catastrophic complication of thrombolysis. Additional studies should assess the net clinical benefit of thrombolysis in high-risk subgroups, particularly the elderly and patients with prior cerebrovascular events.
Preventing Left Ventricular Hypertrophy by ACE Inhibition in Hypertensive Patients With Type 2 Diabetes
Authors: Piero Ruggenenti, Ilian Iliev, Grazia Maria Costa, Aneliya Parvanova, Annalisa Perna, Giovanni Antonio Giuliano, Nicola Motterlini, Bogdan Ene-Iordache, Giuseppe Remuzzi
Journal: Diabetes Care (2008)

In patients with type 2 diabetes, left ventricular hypertrophy (LVH) predicts cardiovascular events, and the prevention of LVH is cardioprotective. We sought to compare the effect of ACE versus non-ACE inhibitor therapy on incident electrocardiographic (ECG) evidence of LVH (ECG-LVH).This prespecified study compared the incidence of ECG-LVH by Sokolow-Lyon and Cornell voltage criteria in 816 hypertensive type 2 diabetic patients of the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT), who had no ECG-LVH at baseline and were randomly assigned to at least 3 years of blinded ACE inhibition with trandolapril (2 mg/day) or to non-ACE inhibitor therapy. Treatment was titrated to systolic/diastolic blood pressure <130/80 mmHg. ECG readings were centralized and blinded to treatment.Baseline characteristics of the two groups were similar. Over a median (interquartile range) follow-up of 36 (24-48) months, 13 of the 423 patients (3.1%) receiving trandolapril compared with 31 of the 376 patients (8.2%) receiving non-ACE inhibitor therapy developed ECG-LVH (hazard ratio [HR] 0.34 [95% CI 0.18-0.65], P = 0.0012 unadjusted, and 0.35 [0.18-0.68], P = 0.0018 adjusted for predefined baseline covariates). The HR was significant even after adjustment for follow-up blood pressure and blood pressure reduction versus baseline. Compared with baseline, both Sokolow-Lyon and Cornell voltages significantly decreased with trandolapril but did not change with non-ACE inhibitor therapy.ACE inhibition has a specific protective effect against the development of ECG-LVH that is additional to its blood pressure-lowering effect. Because ECG-LVH is a strong cardiovascular risk factor in people with hypertension and diabetes, early ACE inhibition may be cardioprotective in this population.
Randomized Controlled Trial of Azacitidine in Patients With the Myelodysplastic Syndrome: A Study of the Cancer and Leukemia Group B
Authors: Lewis R. Silverman, Erin P. Demakos, Bercedis L. Peterson, Alice B. Kornblith, Jimmie C. Holland, Rosalie Odchimar-Reissig, Richard M. Stone, Douglas Nelson, Bayard L. Powell, Carlos M. DeCastro, John Ellerton, Richard A. Larson, Charles A. Schiffer, James F. Holland
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Patients with high-risk myelodysplastic syndrome (MDS) have high mortality from bone marrow failure or transformation to acute leukemia. Supportive care is standard therapy. We previously reported that azacitidine (Aza C) was active in patients with high-risk MDS. PATIENTS AND METHODS: A randomized controlled trial was undertaken in 191 patients with MDS to compare Aza C (75 mg/m 2 /d subcutaneously for 7 days every 28 days) with supportive care. MDS was defined by French-American-British criteria. New rigorous response criteria were applied. Both arms received transfusions and antibiotics as required. Patients in the supportive care arm whose disease worsened were permitted to cross over to Aza C. RESULTS: Responses occurred in 60% of patients on the Aza C arm (7% complete response, 16% partial response, 37% improved) compared with 5% (improved) receiving supportive care (P &lt; .001). Median time to leukemic transformation or death was 21 months for Aza C versus 13 months for supportive care (P = .007). Transformation to acute myelogenous leukemia occurred as the first event in 15% of patients on the Aza C arm and in 38% receiving supportive care (P = .001). Eliminating the confounding effect of early cross-over to Aza C, a landmark analysis after 6 months showed median survival of an additional 18 months for Aza C and 11 months for supportive care (P = .03). Quality-of-life assessment found significant major advantages in physical function, symptoms, and psychological state for patients initially randomized to Aza C. CONCLUSION: Aza C treatment results in significantly higher response rates, improved quality of life, reduced risk of leukemic transformation, and improved survival compared with supportive care. Aza C provides a new treatment option that is superior to supportive care for patients with the MDS subtypes and specific entry criteria treated in this study.
Phase II Clinical Trial of Chemotherapy-Naïve Patients ≥ 70 Years of Age Treated With Erlotinib for Advanced Non–Small-Cell Lung Cancer
Authors: David M. Jackman, Beow Y. Yeap, Neal I. Lindeman, Panos Fidias, Michael S. Rabin, Jennifer Temel, Arthur T. Skarin, Matthew Meyerson, Alison J. Holmes, Ana M. Borras, Boris Freidlin, Patricia A. Ostler, Joan Lucca, Thomas J. Lynch, Bruce E. Johnson, Pasi A. Jänne
Journal: Journal of Clinical Oncology (2007)

This is a phase II, multicenter, open-label study of chemotherapy-naïve patients with non-small-cell lung cancer (NSCLC) and age > or = 70 years who were treated with erlotinib and evaluated to determine the median, 1-year, and 2-year survival. The secondary end points include radiographic response rate, time to progression (TTP), toxicity, and symptom improvement.Eligible patients with NSCLC were treated with erlotinib 150 mg/d until disease progression or significant toxicity. Tumor response was assessed every 8 weeks by computed tomography scan using Response Evaluation Criteria in Solid Tumors. Tumor samples were analyzed for the presence of somatic mutations in EGFR and KRAS.Eighty eligible patients initiated erlotinib therapy between March 2003 and May 2005. There were eight partial responses (10%), and an additional 33 patients (41%) had stable disease for 2 months or longer. The median TTP was 3.5 months (95% CI, 2.0 to 5.5 months). The median survival time was 10.9 months (95% CI, 7.8 to 14.6 months). The 1- and 2- year survival rates were 46% and 19%, respectively. The most common toxicities were acneiform rash (79%) and diarrhea (69%). Four patients developed interstitial lung disease of grade 3 or higher, with one treatment-related death. EGFR mutations were detected in nine of 43 patients studied. The presence of an EGFR mutation was strongly correlated with disease control, prolonged TTP, and survival.Erlotinib monotherapy is active and relatively well tolerated in chemotherapy-naïve elderly patients with advanced NSCLC. Erlotinib merits consideration for further investigation as a first-line therapeutic option in elderly patients.
The Envelope and the Psychiatrist: A Study of Patients' Envelopes
Authors: HARRY A. WILMER
Journal: American Journal of Psychiatry (1967)

The envelope as an imprint of the personality and preconscious thinking of its sender, and as a mirror of the relationship between sender and receiver, is investigated. Its multiple parts (addressee's designation, return address, placement of address, use of background space, type of envelope, postmark, postage stamp) are examined individually. It is suggested that a patient's seriatim sample of envelopes reveals variations which correlate with cinical changes and is therefore a reliable projection device.
New avian model of experimental glomerulonephritis consistent with mediation by cellular immunity. Nonhumorally mediated glomerulonephritis in chickens.
Authors: W K Bolton, F L Tucker, B C Sturgill
Journal: Journal of Clinical Investigation (1984)

The present study examined the role of cell-mediated immunity (CMI) in the production of experimental autoimmune glomerulonephritis (EAG) in chickens deficient in humorally mediated immunity (HMI). Cyclophosphamide bursectomized (Bsx) and normal control chickens were used. Bsx chickens were used only if they had severe depression of HMI, which was evidenced by marked reduction in bursal weights (0.89 +/- 0.23 vs. 2.92 +/- 0.9 g), decreased serum IgG to less than or equal to 10% of normal, and total lack of HMI to immunization with sheep red blood cells. EAG was produced by immunizing chickens with bovine glomerular basement membrane (GBM) in complete Freund's adjuvant. CMI manifested by wattle thickness increments to PPD was not different, 3.89 +/- 0.45 mm for Bsx compared with 3.73 +/- 0.75 mm for controls. No circulating antibodies to GBM developed in 68% of Bsx chickens, and the anti-GBM titers were less than 1:312 in those Bsx chickens positive for antibody compared with greater than 2,000 for controls. GBM deposits of IgG by fluorescence were much decreased, 0.53 +/- 0.16 compared with 2.19 +/- 0.32 for controls, and were absent in 64% of Bsx chickens. Nonetheless, proliferative nephritis with crescents was present and was even more severe in Bsx chickens than in controls, with glomerular sizes of 20.8 +/- 0.6 U for Bsx-GBM, 19.8 +/- 1.2 for control-GBM, 14.9 +/- 1.5 for Bsx, and 13.6 +/- 0.8 for normal chickens. Nephritic eluates did not produce disease in normal chickens, while administration of sensitized cells with [H3]thymidine to naive birds was associated with increased mesangial grain counts by autoradiography. These findings suggest that CMI plays a major role in the pathogenesis of EAG in chickens in the absence of HMI. By implication, CMI may be crucial in the development of other types of glomerulonephritis as well.
MicroRNA-Mediated In Vitro and In Vivo Direct Reprogramming of Cardiac Fibroblasts to Cardiomyocytes
Authors: Tilanthi M. Jayawardena, Bakytbek Egemnazarov, Elizabeth A. Finch, Lunan Zhang, J. Alan Payne, Kumar Pandya, Zhiping Zhang, Paul Rosenberg, Maria Mirotsou, Victor J. Dzau
Journal: Circulation Research (2012)

Rationale: Repopulation of the injured heart with new, functional cardiomyocytes remains a daunting challenge for cardiac regenerative medicine. An ideal therapeutic approach would involve an effective method at achieving direct conversion of injured areas to functional tissue in situ. Objective: The aim of this study was to develop a strategy that identified and evaluated the potential of specific micro (mi)RNAs capable of inducing reprogramming of cardiac fibroblasts directly to cardiomyocytes in vitro and in vivo. Methods and Results: Using a combinatorial strategy, we identified a combination of miRNAs 1, 133, 208, and 499 capable of inducing direct cellular reprogramming of fibroblasts to cardiomyocyte-like cells in vitro. Detailed studies of the reprogrammed cells demonstrated that a single transient transfection of the miRNAs can direct a switch in cell fate as documented by expression of mature cardiomyocyte markers, sarcomeric organization, and exhibition of spontaneous calcium flux characteristic of a cardiomyocyte-like phenotype. Interestingly, we also found that miRNA-mediated reprogramming was enhanced 10-fold on JAK inhibitor I treatment. Importantly, administration of miRNAs into ischemic mouse myocardium resulted in evidence of direct conversion of cardiac fibroblasts to cardiomyocytes in situ. Genetic tracing analysis using Fsp1Cre-traced fibroblasts from both cardiac and noncardiac cell sources strongly suggests that induced cells are most likely of fibroblastic origin. Conclusions: The findings from this study provide proof-of-concept that miRNAs have the capability of directly converting fibroblasts to a cardiomyocyte-like phenotype in vitro. Also of significance is that this is the first report of direct cardiac reprogramming in vivo. Our approach may have broad and important implications for therapeutic tissue regeneration in general.
To know or not to know: archiving and the under-appreciated historical value of data
Authors: David Covarrubias, Maurice Van Emburgh, Hassan R Naqvi, Christian Schmidt, Shawn Mathur
Journal: Molecular Cancer (2008)

Abstract Surplus goods, produced by a community, allow individuals to dedicate their efforts to abstract problems, while enjoying the benefits of support from the community. In return, the community benefits from the intellectual work, say, efficiently producing goods or profound medical aid. In further elevating quality of life, we need to understand nature and biology on the most detailed level. Inevitably, research costs are increasing along with the need for more scientists to specialize their efforts. As a result, a vast amount of data and information is generated that needs to be archived and made openly accessible with the permission to re-use and re-distribute. With economies undergoing crises and prosperity in an almost cyclic manner, it seems that funding for science and technology follows a similar pattern. Another aspect to the problem of the loss of data is the human propensity, at the level of each individual researcher, to passively discard data in the course of daily life and through a career. In a typical laboratory, significant amounts of information is still stored on disks in file cabinets or on isolated computers, and is lost when a research group disbands. Being conscientious to one's data, to see that it reaches a place in which it can persist beyond the lifespan of any one individual requires responsibility on the part of its creator.