tbuckley/cabot-search huggingface dataset:
Profile of systemic oxidative stress markers and effect on skeletal muscle function in COPD
Authors: Jonathan Maury, Farès Gouzi, Philippe De Rigal, Joël Pincemail, Pascal Pomies, Christian Prefaut, Maurice Hayot
Journal: European Respiratory Journal (2013)

Oxidative stress is involved in the skeletal muscle dysfunction of patients with COPD. Resting or exercise-induced imbalance between oxidants and antioxidants is common in COPD, but the precise systemic oxidative stress profile remains unclear. This could explain the limited effects reported following antioxidant supplementation. We therefore determined the systemic oxidative profile of stable COPD patients to identify the proportion with an abnormal profile.

We measured the plasma levels of enzymatic and non-enzymatic antioxidants and of lipid peroxidation (LP) markers in 28 stable COPD patients at rest and after a quadriceps endurance test (Qend) at 30% of the maximal strength. Results were compared with the lower and upper limits of reference (LLR and ULR) of a healthy subject cohort.

At rest, the Vitamin C/Vitamin E ratio was decreased in 54% of patients (0.58±0.27; LLR=0.59) and selenium level in 73% (91±14 μg/ml; LLN=94). The Cu/Zn ratio was increased in 79% (1.44±0.31; ULR=1.17). LP level was increased in 64% of patients and significantly correlated with the 6-min walking distance (r=0.60; p<0.005) and muscle mass (r=0.47; p<0.05). After the Qend, Vitamin E and Zn plasma levels decreased in 55% and 91% of patients respectively, without changes in LP level.

Altogether, our findings indicate that in 92% of stable COPD patients, the systemic oxidative stress profile is imbalanced, particularly the concentration of dietary vitamins and trace elements, and is associated with the skeletal muscle dysfunction. This imbalanced profile can be modified by local quadriceps exercise. More patients are needed to identify specific phenotypes of antioxidant deficits.
Is sustained control of severe asthma possible? A composite score to assess 1-year of asthma control
Authors: Arnaud Bourdin, Nicolas Molinari, Laurence Halimi, Grégory Marin, Muriel Varin, Anne Sophe Gamez, Isabelle Vachier, Pascal Chanez
Journal: European Respiratory Journal (2013)

Background : It is still unclear whether sustained control of severe asthma over a 1 year period using the best standard of care, including non-pharmaceutical advice, is possible.

Methods : 62 severe asthma patients were enrolled in a 2-year prospective study. After a 1 year run-in period that confirmed the asthma severity, management was optimized through six visits over the second year, including systematic attention to psychological and therapeutic adherence questions. A composite control score was used that integrated the ACQ score, the FEV1 value and the exacerbation rate at each visit to define optimal (ACQ always   85% best personal values) and acceptable control (ACQ   85% best personal values).

Results : Optimal control was sustained in 9 out of 62 patients (15%) and 8 additional patients (total 28%) had sustained acceptable control. Exacerbations decreased significantly from 3/yr to less than 1/yr (p<0.001). Quality of life at entry was the only independent factor associated with the inability to sustain control (p = 0.019). Female gender and high FEV1 variations over the year were independently associated with annual exacerbations. The ACQ score at each visit was the best predictor of subsequent exacerbations.

Conclusion : Enrolling severe asthma patients in a clinical trial efficiently decreased the exacerbation rate. Achieving sustained control over a 1 year period in severe asthma patients is still a challenge.
Effects of using the 2007 IDSA/ATS minor criteria to manage severe community-acquired pneumonia
Authors: Hui Fang Lim, Jason Phua, Amartya Mukhopadhyay, Wang Jee Ngerng, Malcolm Mahadevan, Tow Keang Lim
Journal: European Respiratory Journal (2013)

Background:  Severe community-acquired pneumonia (SCAP) is associated with mortality rates as high as 50%. Delayed intensive care unit (ICU) admission is associated with increased mortality. Pneumonia severity scores may help in early identification of at-risk SCAP patients. This study aimed to evaluate the clinical impact of using the 2007 IDSA/ATS minor criteria in SCAP.  Methods:  We started using the minor criteria at the emergency department (ED) as a triage tool in 2008. In this cohort study, we categorized patients into control (2004 - 2007) and intervention arms (2008 - 2010). We defined SCAP as fulfilment of ≥3 minor criteria regardless of site of care. We compared the site of care, route of ICU admission and hospital mortality. Patients with ≤2 minor criteria but required ICU admission were evaluated separately.  Results:  There were 172 and 176 ICU admissions in the control and intervention arms respectively. The proportion of SCAP patients admitted to the ICU decreased from 52.9% to 38.6% (p=0008). Of those who required ICU admission, direct admissions increased from 39.6% to 61.8% (p=0.006). Hospital mortality decreased from 23.8% to 5.7% (p  There were 65 and 63 patients with ≤2 minor criteria requiring ICU admission in the control and intervention arms; ICU admission rates were 18.5% and 46.0% respectively.  Conclusion  Use of the 2007 IDSA/ATS minor criteria for triage may increase direct ICU admissions and reduce mortality in at-risk SCAP patients. It may not result in treatment delay in patients with ≤2 minor criteria and may not increase ICU admission rates.
Predictors of lipoprotein particle size and subclasses in patients with OSA
Authors: Radovan Tisko, Zorana Jelic-Ivanovic, Viera Habalova, Zuzana Sopkova, Eva Slaba, Jelena Vekic, Zuzana Dorkova, Aleksandra Zeljkovic, Pavol Joppa, Manfredi Rizzo, Ruzena Tkacova
Journal: European Respiratory Journal (2013)

Rationale:  Apolipoprotein E ( APOE ) gene polymorphism is related to atherogenic dyslipidemia, and may play a role in affecting low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) size and subclasses distribution. Importantly, intermittent hypoxia increases serum lipids in APOE-deficient mice. Previously we have demonstrated atherogenic dyslipidemia and reduced LDL size in patients with obstructive sleep apnea (OSA). Here we aimed to analyze the effects of  APOE  gene polymorphisms on LDL and HDL size and subclasses in patients with OSA.   Methods:  189 adult subjects underwent full overnight polysomnography. The association of HDL-C and LDL-C size and subclasses with apnea-hypopnea index (AHI), oxygen desaturation index (ODI) and arousal index, and with  APOE  gene polymorphism was examined and adjusted for relevant covariates.   Findings:  Patients were 61.4% male (age 51.7±12.0 years, AHI 29.5±30.1 events/hour). LDL-C size was related to  APOE  polymorphism (p=0.024), due to a reduction in large LDI-I particles and increase in small dense LDL-IVB particles. In addition, LDL-C size was related to ODI, AHI and arousal index in univariate analyses (r=-0.136, p=0.028; r=-0.172, p=0.005; r=-0.132, p=0.032; respectively). In contrast, HDL-C size was related to AHI only (r= 0.137, p=0.026). In multivariate analysis, only  APOE  genotype predicted LDL-C size independently of age, gender, body mass index and severity of OSA (R2=0.095, p=0.013).   Conclusion:  Our results suggest relationships between  APOE  gene polymorphism and LDL-C size in patients with OSA. Further studies are needed to evaluate clinical implications of present findings.   Funding:  APVV-0134-11, VEGA 1/0111/12, Slovakia.
Cigarette Smoke–induced Oxidative Stress
Authors: Esther Barreiro, Víctor I. Peinado, Juan B. Galdiz, Elisabet Ferrer, Judith Marin-Corral, Francisco Sánchez, Joaquim Gea, Joan Albert Barberà
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Inflammation and oxidative stress contribute to muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD). Oxidants contained in cigarette smoke (CS) induce adverse effects on tissues through oxidative phenomena.To explore oxidative stress and inflammation in quadriceps of human smokers and in diaphragm and limb muscles of guinea pigs chronically exposed to CS.Muscle function, protein oxidation and nitration, antioxidants, oxidized proteins, inflammation, creatine kinase activity, and lung and muscle structures were investigated in vastus lateralis of smokers, patients with COPD, and healthy control subjects and in diaphragm and gastrocnemius of CS-exposed guinea pigs at 3, 4, and 6 months.Compared with control subjects, quadriceps muscle force was mildly but significantly reduced in smokers; protein oxidation levels were increased in quadriceps of smokers and patients with COPD, and in respiratory and limb muscles of CS-exposed animals; glycolytic enzymes, creatine kinase, carbonic anydrase-3, and contractile proteins were significantly more carbonylated in quadriceps of smokers and patients with COPD, and in respiratory and limb muscles of CS-exposed guinea pigs. Chronic CS exposure induced no significant rise in muscle inflammation in either smokers or rodents. Muscle creatine kinase activity was reduced only in patients with COPD and in both diaphragm and gastrocnemius of CS-exposed animals. Guinea pigs developed bronchiolar abnormalities at 4 months of exposure and thereafter.CS exerts direct oxidative modifications on muscle proteins, without inducing any significant rise in muscle inflammation. The oxidative damage to muscle proteins, which precedes the characteristic respiratory changes, may contribute to muscle loss and dysfunction in smokers and patients with COPD.
Prognostic value of urokinase plasminogen activator receptor (uPAR) and neutrophil CD64 expression in acute respiratory distress syndrome patients
Authors: Adel Attia, Huda Hassan, Mohammed Elsammak
Journal: European Respiratory Journal (2013)

The outcome of acute respiratory distress syndrome (ARDS) may vary from complete recovery to multiorgan failure and death. The current study evaluates the prognostic performance of plasma uPAR and Neutrophil expression of CD64 in patients with ARDS of different etiologies and tests the possible correlation with other prognostic markers, namely APACHE-II score and serum CRP. The current study included 2 groups: 68 patients with ARDS and 25 age- and sex-matched, randomly selected, healthy control subjects. Blood samples were taken for routine laboratory tests on admission to ICU. Plasma uPAR was measured using a commercially available ELISA kit, and neutrophil CD64 expression was measured using fow cytometry. Plasma uPar was signifcantly higher in bacteremic ARDS patients than those without bacteremia. There was also a signifcant increase in plasma uPAR in ARDS survivors than in those who died. CD64 expression showed a similar pattern of increase in bacteremic ARDS. Using ROC curves plasma uPAR outperformed CD64 expression and CRP as a prognostic indicator in the studied ARDS patients. A cut-off value for plasma uPAR which almost always predicted mortality was 15.1ng/ml with PPV of 100% and NPV 97%. Plasma uPAR is signifcantly elevated in ARDS patients and has a superior prognostic value to both neutrophil CD64 expression and serum CRP in ARDS patients. A plasma uPAR cutoff value of 15.1ng/ml has a PPV of 100% and NPV of 97% in predicting mortality in the ARDS patient included in the current study.
Sequence of Deposition of Amyloid in Strain A Mice and Relationship to Renal Disease2
Authors: William T. West, Edwin D. Murphy
Journal: JNCI Journal of the National Cancer Institute (1965)

Journal Article Sequence of Deposition of Amyloid in Strain A Mice and Relationship to Renal Disease Get access William T. West, William T. West The Jackson Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar Edwin D. Murphy Edwin D. Murphy The Jackson Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 35, Issue 1, July 1965, Pages 167–174, https://doi.org/10.1093/jnci/35.1.167 Published: 01 July 1965 Article history Received: 21 January 1965 Published: 01 July 1965
The changing indications for IGRA testing and impact on TB services in a UK district general hospital
Authors: Sam Roberts, Paul Godwin, Janet Anderson, Harold Stephen Ronald Hosker
Journal: European Respiratory Journal (2013)

To assess the impact of interferon gamma release assay (IGRA) testing in a rural UK hospital we retrospectively examined IGRA tests at our laboratory from 2006-2012. Indication and outcome of testing was determined.  Of 899 T-SPOT tests, 377 were for investigation of possible active TB. 507 were screening tests for latent TB infection (LTBI). Of these, 329 were prior to monoclonal antibody (mAb) treatment, 101 for contact tracing or new entrants, and 77 as occupational health assessments.  Total tests per year did not significantly change between 2008 (179) and 2012 (152). Tests pre-mAb treatment increased (0 in 2006, 55 in 2009, 87 in 2012) leading to increasing referrals to TB services. From 2006-2008, 2 patients received TB chemoprophylaxis (CPX) pre-mAb. This increased to 10 in 2009-2011. Total numbers receiving CPX increased from 7 in 2005 to a peak of 19 in 2010. The mean age of those screened pre-mAb therapy was 54 years compared to 34 for contact and new entrant screening (p=   There were rises in both pre-mAb screening and resulting CPX usage. The increased sensitivity of T-SPOT compared to skin testing for screening of contacts may have partially offset the overall rise in CPX usage.  Screening pre-mAb therapy resulted in a higher proportion of older patients referred for treatment. This raises potential concerns regarding CPX in those at higher risk of hepatotoxicity.  We conclude that increasing use of biological agents is resulting in an increase in diagnosis and treatment of LTBI. This has impact both for patients and planning of TB services. The age profile of those requiring chemoprophylaxis may change as result of the changing indications for testing.
Predicting Prognosis in Chronic Lymphocytic Leukemia in the Contemporary Era
Authors: Chadi Nabhan, Gordana Raca, Y. Lynn Wang
Journal: JAMA Oncology (2015)

Next-generation sequencing has identified new genetic markers that have altered prognosis for patients with chronic lymphocytic leukemia (CLL) at diagnosis. Understanding the significance of these prognostic indicators and recognizing their potential impact on treatment selection and patients' outcomes is critical for clinicians and investigators.To review novel prognostic factors at CLL diagnosis that have shown an impact on the prognosis and outcomes of this disease.Literature from January 2004 through December 2014 was searched in PubMed, Cochrane Central Register of Controlled Trials, and Scopus to identify English-language, peer-reviewed articles on clinical and prognostic factors for CLL (TP53, ATM, NOTCH1, SF3B1, BIRC3, and MYD88). Reference lists were subsequently reviewed for additional articles. A total of 450 articles was identified, and 48 articles meeting inclusion criteria were reviewed.Among prognostic markers reviewed, chromosomal aberrations have been validated and are currently used clinically to predict prognosis. Patients with 17p13.1 deletion have poor response to chemoimmunotherapy and are treated differently, with some undergoing allogeneic transplantation in first remission. CD38 and ZAP-70 status of malignant cells and unmutated immunoglobulin variable heavy chain gene have similarly been validated to predict adverse prognosis, but their implications on treatment selection have not been proven. The presence of TP53 and ATM mutations predicts worse prognosis, which has been corroborated in various studies. Patients with TP53 mutations have lower responses to chemoimmunotherapy. Furthermore, patients with TP53 and ATM mutations have inferior progression-free survival and overall survival, independent of other factors. Patients carrying the NOTCH1 and SF3B1 mutations have worse prognosis; patients with the NOTCH1 mutation have lower response rates to standard chemoimmunotherapy. The impact of BIRC3 on prognosis and survival requires further confirmation.The heterogeneous clinical course of CLL is likely explained by underlying molecular prognostic factors. Moving forward, analyzing these factors at diagnosis is recommended for better prognostication.
High performance and timely care of integrated FDG-PET and diagnostic CT in a rapid outpatient diagnostic program for suspected lung cancer patients
Authors: Pepijn Brocken, Hendrikus Van der Heijden, Richard Dekhuizen, Liesbeth Peters-Bax, Lioe-Fee De Geus-Oei
Journal: European Respiratory Journal (2012)

INTRODUCTION   The objective of this study was to evaluate the diagnostic performance of  18 F-fluorodeoxy-glucose-Positron Emission Tomography with integrated contrast enhanced Computed Tomography (FDG-PET/CT) as a routine diagnostic tool in a Rapid Outpatient Diagnostic Program (RODP) for patients referred on the basis of a chest X-ray suspicious of lung cancer.   METHODS   A retrospective chart study was conducted of all patients referred to the two-day RODP of our tertiary care university clinic between 1999 and 2009 after an abnormal chest X-ray. We analyzed timeliness of care and the diagnostic performance of FDG-PET/CT to differentiate between malignant and benign lesions.   RESULTS   In 386 patients available for analysis, 260 patients were diagnosed with non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) of both subtypes; 23 patients had another type of malignancy, 78 patients had certain benign disease, and in 45 patients the diagnosis was not pathologically confirmed but a median 24.5 months follow up confirmed a benign outcome. Sensitivity, specificity, negative predictive value, positive predictive value and accuracy of FDG-PET/CT to differentiate lung cancer from benign disease were 97.7%, 60.2%, 92.5%, 84.0% and 85.7% respectively. For lung cancer patients, median referral time was seven days, diagnostic delay was 2 days and therapeutic delay 19 days.   CONCLUSION   FDG-PET/CT in an RODP setting for suspected lung cancer has high performance in detecting cancer and facilitates timely care.
Alpha-Adrenoceptor Modulation in Central Nervous System Trauma: Pain, Spasms, and Paralysis - An Unlucky Triad
Authors: Stefanie Lemmens, Bert Brône, Dearbhaile Dooley, Sven Hendrix, Nathalie Geurts
Journal: Medicinal Research Reviews (2014)

Many researchers have attempted to pharmacologically modulate the adrenergic system to control locomotion, pain, and spasms after central nervous system (CNS) trauma, although such efforts have led to conflicting results. Despite this, multiple studies highlight that α-adrenoceptors (α-ARs) are promising therapeutic targets because in the CNS, they are involved in reactivity to stressors and regulation of locomotion, pain, and spasms. These functions can be activated by direct modulation of these receptors on neuronal networks in the brain and the spinal cord. In addition, these multifunctional receptors are also broadly expressed on immune cells. This suggests that they might play a key role in modulating immunological responses, which may be crucial in treating spinal cord injury and traumatic brain injury as both diseases are characterized by a strong inflammatory component. Reducing the proinflammatory response will create a more permissive environment for axon regeneration and may support neuromodulation in combination therapies. However, pharmacological interventions are hindered by adrenergic system complexity and the even more complicated anatomical and physiological changes in the CNS after trauma. This review is the first concise overview of the pros and cons of α-AR modulation in the context of CNS trauma.
Abstract 17174: Predictors of Stent Thrombosis after Everolimus-Eluting and Paclitaxel-Eluting Stents: The Pooled SPIRIT Randomized Trial Experience at Two Years of Follow-Up
Authors: Ajay Kirtane, Poornima Sood, Robert J Applegate, Manejeh Yaqub, Yoshinobu Onuma, John C Wang, Xiaolu Su, Karine Miquel-Hebert, Alexandra J Lansky, Dean J Kereiakes, Charles A Simonton, Krishnankutty Sudhir, Patrick W Serruys, Gregg W Stone
Journal: Circulation (2010)
Long-term fertility and Leydig cell function in patients treated for germ cell cancer with cisplatin, vinblastine, and bleomycin versus surveillance.
Authors: S W Hansen, J G Berthelsen, H von der Maase
Journal: Journal of Clinical Oncology (1990)

Fertility and Leydig cell function were investigated in 31 patients previously treated for nonseminomatous testicular cancer. Twenty-two patients with metastatic cancer had received cisplatin-based chemotherapy, and the median follow-up was 64 months (range, 42 to 100 months). Nine patients without metastases were treated with orchiectomy alone, and follow-up in this group was a median of 61 months (range, 40 to 77 months). None of the patients have relapsed and retroperitoneal lymph node dissection was not performed in any patient. Both the concentration of spermatozoa and the volume of the remaining testis are significantly reduced in patients who had previously received chemotherapy when compared with patients treated with orchiectomy alone (P less than .05). There were no significant differences between groups when comparing morphology, motility, and penetration of the spermatozoa. Subclinical Leydig cell dysfunction with normal testosterone and elevated luteinizing hormone (LH) was observed in one patient (11%) treated with orchiectomy alone, while 59% of the patients who had received chemotherapy had elevated LH (P less than .05). We conclude that cisplatin-based chemotherapy leads to a persistent impairment of fertility and Leydig cell function in the majority of patients with testicular cancer.
DEAE-dextran MMA copolymer non-viral vector for aerosol therapy in respiratory diseases
Authors: Kaid Darwiche, Paul Zarogoulidis, Christos Ritzoulis, Wolfgang Hohenforst-schmidt, Leonidas Sakkas, Aggeliki Cheva, Antonios Sakkas, Dionysios Spyratos, Dora Sparopoulou, Konstantinos Zarogoulidis
Journal: European Respiratory Journal (2013)

The new non-viral vector DDMC (DEAE-dextran MMA copolymer) was purchased by Ryujyu science corporation from Tokyo and was tested for safety in BALBC mice. A [maxined] compressor nebulizer was used to aerosolize 1ml/11ml in 5 minutes. The size distribution of the solution droplets was determined using a Malvern Mastersizer 2000 laser scattering apparatus (Malvern) equipped with a Scirocco module (Malvern,). The latter was modified as for the dispersion to be sprayed directly into the sample chamber, normal to the laser beam. A refractive index of 1.33 was used for the dispersed phase. In ten mice the non-viral vector was delivered every 3 days for 24 days. Ten mice were control A. Three mice were sacrificed after 12 days B. The rest of the 7 mice were sacrificed after the final inhalation on day 24 C. Emphysema was observed (Figure 1), but without any damage macroscopically (Figure 2). The control group mice were also sacrificed all ten on day 24, with no damage macroscopically, or histopathologically.  This non-viral vector was designed specifically for aerosol gene administration however induced lung emphysema in the BALBC mice and is therefore not suitable as a vehicle.